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Sample records for lilli paarma hannu

  1. LY-354740 (Eli Lilly).

    Science.gov (United States)

    Pilc, Andrzej

    2003-01-01

    Lilly is developing LY-354740, the lead compound in a series of derivatives of the metabotropic glutamate receptor group II agonist L-CCG-1, for the potential treatment of anxiety [212536], [276941], [276942].

  2. Ruboxistaurin (Eli Lilly).

    Science.gov (United States)

    Wheeler, Glen D

    2003-02-01

    Eli Lilly & Co is developing the protein kinase C (PKC)-b inhibitor ruboxistaurin, the lead compound from a series of 14-membered macrocycles, for the potential treatment of diabetic retinopathy, diabetic peripheral neuropathy and macular edema.

  3. Drotrecogin alfa Eli Lilly

    NARCIS (Netherlands)

    de Jonge, E.

    2002-01-01

    Drotrecogin alfa (Xigris, recombinant activated protein C) is an anticoagulant developed and launched by Eli Lilly & Co for the treatment of sepsis [333781], [339372], [430133], [436271]. The FDA and the EMEA accepted the brand name Xigris for drotrecogin alfa in June 2001. This trade name had been

  4. Fasidotril Eli Lilly.

    Science.gov (United States)

    Ozdener, Fatih; Ozdemir, Vural

    2003-09-01

    Lilly is developing fasidotril, a diester prodrug of the active metabolite fasidotrilat, for the potential treatment of hypertension and congestive heart failure (CHF). Phase II trials to investigate the potential of fasidotril for the treatment of hypertension and CHF had commenced by the late 1990s, and were ongoing in July 2003 in the US and Europe.

  5. Drotrecogin alfa Eli Lilly.

    Science.gov (United States)

    de Jonge, E

    2002-04-01

    Drotrecogin alfa (Xigris, recombinant activated protein C) is an anticoagulant developed and launched by Eli Lilly & Co for the treatment of sepsis [333781], [339372], [430133], [436271]. The FDA and the EMEA accepted the brand name Xigris for drotrecogin alfa in June 2001. This trade name had been proposed by Lilly in place of the previous brand name, Zovant, which was deemed unacceptable by the EMEA due to concerns that the name could be confused with hospital-based drugs [412512]. Filings for sepsis were made in the US, EU and Australia in February 2001 [398514], [447870] and in March 2001, the US FDA assigned drotrecogin alfa Priority Review status [403435]. The FDA extended the action date from July 27 to October 27, 2001 for completion of its review of the biologics license application (BLA) for drotrecogin alfa to assess further supplementary data submitted by Lilly [412512]. At the October 16, 2001 meeting (postponed from September 12), the FDA Advisory Committee on Anti-Infective Drugs split 10 to 10 over whether to recommend approval [425873], [425940]. In late October 2001, Lilly received an approvable letter from the FDA for the treatment of severe sepsis. Approval was contingent upon successful negotiation of labeling, agreement on post-approval clinical trials, and successful completion of manufacturing inspections [427301]. In November 2001, the FDA approved drotrecogin alfa for the reduction of mortality in adult patients with severe sepsis who have a high risk of death [430133]; the product was launched onto the US market days later [436271]. Following the FDA committee's split decision in October 2001, Credit Suisse First Boston, which expected mid-2002 approval but with restrictive labeling, revised its predictions from $1.265 billion in 2004 sharply downwards to $543 million [425929].

  6. Duloxetine Eli Lilly & Co.

    Science.gov (United States)

    Pitsikas, N

    2000-09-01

    Lilly is developing duloxetine, a 5-HT and norepinephrine uptake inhibitor as a potential treatment for depression and urinary incontinence. In Japan, it is being jointly developed with Shionogi [187401]. Phase III trials for depression and phase II trials for urinary incontinence are underway in Japan [296442,328887]. Lilly expects to file for depression in 2002 and phase III trials for urinary incontinence are planned to start enrollment by the end of 2000 [358429,370526,373870]. Duloxetine has a half-life of 10 to 15 h in humans, and parameters reach a steady-state after 3 days of daily administration. In a 6-week, open-label study duloxetine was safe and well tolerated in 79 clinically depressed patients. Clinical response occurred in 78% of patients, and remission occurred in 60%. Insomnia and nausea occurred with an incidence of 20% [300881]. Duloxetine may offer advantages over existing antidepressants, such as Lilly's fluoxetine, because of faster recovery and fewer side effects [190226]. In June 2000, Morgan Stanley Dean Witter predicted duloxetine would reach the market in 2002 with annual sales in this year of US $50 million, rising to $200 million in 2005 [373870]. In February 1999, Deutsche Bank predicted Lilly's sales at US $200 million in 2002 rising to $400 million in 2003 [316821]. In May 2000, Deutsche Bank had made further predictions, stating that filing for duloxetine is expected in the fourth quarter of 2001, and peak sales are expected to exceed US $500 million. Also in February 1999, Lehman Brothers predicted the first major launch date (US and ex-US) to be 2002, with the year of peak sales to be 2008 [319225]. In August 1999, this prediction changed, and the expected launch date became 2001, with an 80% probability of reaching the market and sales peaking at US $150 million in 2012 [349228].

  7. Anidulafungin (Eli Lilly & Co).

    Science.gov (United States)

    Hawser, S

    1999-12-01

    The pentyloxyterphenyl side chain derivative of echinocandin B, anidulafungin, is a 1,3-alpha-glucan synthesis inhibitor undergoing phase II clinical trials by Versicor and Eli Lilly, in various formulations, for the potential treatment of fungal and protozoal infections. Eli Lilly has retained options to the oral formulation of the compound, but development, clinical registration and marketing rights were licensed to Versicor in June 1999. The primary target of this compound is Candida, but Eli Lilly also intends to develop the drug for Aspergillus infections. No activity has been shown against Cryptococcus. The oral activity of anidulafungin is compromised by a low bioavailability, a decreased absorption when taken with food, and gastrointestinal side effects at higher doses. The development of a phosphorylated prodrug, LY-307853, which is converted in the body to anidulafungin by tissue and serum phosphatases, was discontinued in favor of an oral formulation, which uses anidulafungin directly. In February 1999, Deutsche Bank predicted sales of $100 million in 2001, rising to $300 million in 2003.

  8. Tomoxetine (Eli Lilly & Co).

    Science.gov (United States)

    Preti, Antonio

    2002-02-01

    Eli Lilly is developing tomoxetine, a norepinephrine reuptake inhibitor, for the potential treatment of attention deficit hyperactivity disorder (ADHD) and depression. As of May 2000, tomoxetine was undergoing phase III trials in the US [368128]. An NDA was filed with the FDA in October 2001, with a launch expected in the second half of 2002 [426786]. Tomoxetine was first investigated by Lilly in the 1980s as a potential treatment for depressive illness. The compound was selected from a series of potent inhibitors of norepinephrine reuptake, and reached large-scale phase II clinical trials for depression in 1990. Development for this indication appeared to stop at that time, despite some evidence that tomoxetine wasfairly effective [273943]. In 1996, Lilly apparently restarted preclinical development of tomoxetine as a potential therapyfor ADHD, and submitted EP-00721777 claiming tomoxetine's utility for this disorder in July of that year [273956]. In June 2001, ABN AMRO predicted sales of $121 million in 2002, rising to $4,064 million in 2012 [422762]. In October 2001, analysts at Salomon Smith Barney predicted that the product would make sales of $24 million in 2002, rising to $305 million in 2005 [427501].

  9. Oritavancin. Eli Lilly & Co.

    Science.gov (United States)

    Barrett, J F

    2001-08-01

    Oritavancin (LY-333328), a lead glycopeptide from a series targeted at vancomycin-resistant bacteria, especially enterococci, is under development by Eli Lilly for the potential treatment of bacterial infections. It entered phase III trials in the US in January 2001 [396223] and the company expects to submit an NDA by 2003 [396478]. Oritavancin has been reported to have activity comparable to that of vancomycin and teicoplanin (Aventis Pharma AG), but retains activity against glycopeptide-resistant bacterial strains [407519]. The bactericidal activity of oritavancin suggests that it may prove useful as a single agent therapy in the treatment of antibiotic-resistant enterococci. Although its mechanism of action is unclear, dimerization of the glycosyl portion stabilizing D-Ala-D-Ala binding has been suggested [337644].

  10. Pemetrexed disodium (Eli Lilly).

    Science.gov (United States)

    Norman, P

    2001-11-01

    Pemetrexed, a thymidylate synthase (TS) and transferase inhibitor, is in phase III trials with Eli Lilly as a potential treatment for several common solid tumors, including non-small cell lung cancer (NSCLC) and mesothelioma [321789], [410731]. Studies on pemetrexed have concluded that not only is the compound a TS inhibitor but also a potent inhibitor of human dihydrofolate reductase (DHFR). The results suggest that pemetrexed acts upon multiple intracellular targets and that the antitumor effect may be derived from its simultaneous inhibition of multiple folate-requiring enzymes [203662]: this compound has been designated as a multitargeted antifolate (MTA) [386680]. The drug also causes concentration- and time-dependent apoptosis [284380]. Other studies in which the 4-oxo group of the pyrimidine ring portion of pemetrexed was replaced with a hydrogen atom, demonstrated that the resulting analogs were potent DHFR inhibitors with very little activity against the enzymes glycinamide ribonucleotide formyltransferase (GARFT) and TS [310674]. In phase II European studies in 64 patients with advanced breast cancer, encouraging responses were seen in anthracycline-failure (23%) and anthracycline-refractory (19%) patients. Responses were observed in 28% of patients who had been previously treated with a taxane [326097]. Data from a phase II trial of pemetrexed (500 mg/m2 once every 21 days as a 10 min i.v. infusion) as a salvage therapy in advanced breast cancer showed that supplementation of the treatment regime with folic acid (FA) and vitamin B12 reduced its already manageable and tolerable toxicities [408821], [409650]. At doses of 500 mg/m2, the drug was also safely administered to 35 patients with impaired renal function [409953]. Phase I and II trials have shown that the main side effects include neutropenia, thrombocytopenia, mucositis, nausea and vomiting [203666], [272241]. Princeton University holds the patent rights to this drug under EP-00432677. In June

  11. Duloxetine Eli Lilly.

    Science.gov (United States)

    Anttila, Sami; Leinonen, Esa

    2002-08-01

    Duloxetine is a serotonin (5-HT) and norepinephrine (NE) uptake inhibitor in pre-registration for depression. In vivo studies demonstrate that duloxetine inhibits 5-HT and NE transporters and this may induce an antidepressant effect [159168]. In humans, duloxetine has a low affinity for most 5-HT subtypes and for muscarinic, histamine H1, alpha1-adrenergic, alpha2-adrenergic and dopamine D2 receptors [444103]. Thus, it is not surprising that the meta-analysis of four recent clinical studies suggests duloxetine is a potent and well-tolerated antidepressant [429723]. By December 2001, Lilly had filed an NDA for depression. The launch of duloxetine is planned for the second half of 2002 [434250], [436220]. In April 2002, filing for stress urinary incontinence was anticipated for later in 2002 [456894]. Analysts at Banc of America predicted in April 2002, that the drug will be launched in the first quarter of 2003. The company projects US $400 million in revenue in 2003 and anticipates duloxetine to reach peak sales of over US $1 billion [450920]. Analysts at Morgan Stanley, projected US $25 million in sales in the fourth quarter 2002, rising to US $900 million in 2006 [450937]. At the same time, Credit Suisse First Boston anticipated launch for late 2002, with US $220 million in duloxetine revenues in 2003 and US $457 million in 2004 [450936].

  12. LY-293558. Eli Lilly & Co.

    Science.gov (United States)

    Gilron, I

    2001-09-01

    Lilly is developing the racemic compound LY-215490, a selective and competitive AMPA antagonist, as a potential treatment for cerebral infarction, cerebrovascular ischemia, epilepsy and as an analgesic [135089], [158980], [254029], [278691]. By January 2000, LY-293558 was undergoing phase II trials for pain [414000].

  13. Exenatide. Amylin/Eli Lilly.

    Science.gov (United States)

    Giannoukakis, Nick

    2003-04-01

    Amylin Pharmaceuticals Inc and Eli Lilly & Co are co-developing exenatide (AC-2993; synthetic exendin-4), a 39-amino acid, glucagon-like peptide-1 agonist derived from the venom of the Gila monster lizard (Heloderma suspectum) as a potential injectable treatment for type 2 diabetes. The first phase III trial (exenatide as a monotherapy) was initiated in December 2001. In January 2002 the second phase III trial, of exenatide in conjunction with sulfonylureas, was initiated and in March 2002, Amylin initiated the third phase III trial, of exenatide in combination with metformin and sulfonylureas.

  14. Eflucimibe. Pierre Fabre/Eli Lilly.

    Science.gov (United States)

    Burnett, John R

    2003-03-01

    Eflucimibe is an acyl coenzyme A:cholesterol acyltransferase inhibitor under development by Pierre Fabre SA and Eli Lilly & Co for the potential treatment of hypercholesterolemia and atherosclerosis. Phase II clinical trials commenced during 2002.

  15. Luubi all : www.lilly.com / Piret Potisepp

    Index Scriptorium Estoniae

    Potisepp, Piret

    2009-01-01

    Ravimifirma Eli Lilly & Company kogemusi, kuidas uusimate teadusuuringute tulemusi ravimitööstuses kasutades on võimalik arendada jätkusuutlikku tootmist ning laiendada tooteportfelli koostöövõrgustiku kujundamise teel

  16. 78 FR 33426 - Eli Lilly and Co.; Withdrawal of Approval of a New Drug Application for ORAFLEX

    Science.gov (United States)

    2013-06-04

    ...] Eli Lilly and Co.; Withdrawal of Approval of a New Drug Application for ORAFLEX AGENCY: Food and Drug... new drug application (NDA) for ORAFLEX (benoxaprofen) Tablets, held by Eli Lilly and Co. (Lilly), Lilly Corporate Center, Indianapolis, IN 46285. Lilly has voluntarily requested that approval of this...

  17. Modern nonparametric, robust and multivariate methods festschrift in honour of Hannu Oja

    CERN Document Server

    Taskinen, Sara

    2015-01-01

    Written by leading experts in the field, this edited volume brings together the latest findings in the area of nonparametric, robust and multivariate statistical methods. The individual contributions cover a wide variety of topics ranging from univariate nonparametric methods to robust methods for complex data structures. Some examples from statistical signal processing are also given. The volume is dedicated to Hannu Oja on the occasion of his 65th birthday and is intended for researchers as well as PhD students with a good knowledge of statistics.

  18. Eli Lilly and Company's bioethics framework for human biomedical research.

    Science.gov (United States)

    Van Campen, Luann E; Therasse, Donald G; Klopfenstein, Mitchell; Levine, Robert J

    2015-11-01

    Current ethics and good clinical practice guidelines address various aspects of pharmaceutical research and development, but do not comprehensively address the bioethical responsibilities of sponsors. To fill this void, in 2010 Eli Lilly and Company developed and implemented a Bioethics Framework for Human Biomedical Research to guide ethical decisions. (See our companion article that describes how the framework was developed and implemented and provides a critique of its usefulness and limitations.) This paper presents the actual framework that serves as a company resource for employee education and bioethics deliberations. The framework consists of four basic ethical principles and 13 essential elements for ethical human biomedical research and resides within the context of our company's mission, vision and values. For each component of the framework, we provide a high-level overview followed by a detailed description with cross-references to relevant well regarded guidance documents. The principles and guidance described should be familiar to those acquainted with research ethics. Therefore the novelty of the framework lies not in the foundational concepts presented as much as the attempt to specify and compile a sponsor's bioethical responsibilities to multiple stakeholders into one resource. When such a framework is employed, it can serve as a bioethical foundation to inform decisions and actions throughout clinical planning, trial design, study implementation and closeout, as well as to inform company positions on bioethical issues. The framework is, therefore, a useful tool for translating ethical aspirations into action - to help ensure pharmaceutical human biomedical research is conducted in a manner that aligns with consensus ethics principles, as well as a sponsor's core values.

  19. The good gift: a comparison of the Eli Lilly presentation copies of Aequanimitas.

    Science.gov (United States)

    Kimbrough, R C

    1995-08-01

    The Eli Lilly Pharmaceutical Company of Indianapolis, Indiana distributed some 150,000 copies of the third edition of Sir William Osler's Aequanimitas to graduating medical students between 1932 and 1953. Bibliophiles have considered these volumes identical. However, there were at least seven different printings in English and one in Spanish and one in Portuguese. The size of the book and type of paper changed over the years. The title page, spine information, and printing information also changed. A congratulatory letter from Eli Lilly and Company was placed in the front of each book. These letters have many differences. Thus, the volumes are not identical and the recognition of these differences opens a new field for research and collecting.

  20. The development of molecularly targeted anticancer therapies: an Eli Lilly and Company perspective.

    Science.gov (United States)

    Perry, William L; Weitzman, Aaron

    2005-03-01

    The ability to identify activated pathways that drive the growth and progression of cancer and to develop specific and potent inhibitors of key proteins in these pathways promises to dramatically change the treatment of cancer: A patient's cancer could be characterized at the molecular level and the information used to select the best treatment options. The development of successful therapies not only requires extensive target validation, but also new approaches to evaluating drug efficacy in animal models and in the clinic compared to the development of traditional cytotoxic agents. This article highlights Eli Lilly and Company's approach to developing targeted therapies, from target identification and validation through evaluation in the clinic. A selection of drugs in the Lilly Oncology pipeline is also discussed.

  1. John Lilly, The Mind of the Dolphin, and Communication Out of Bounds

    Directory of Open Access Journals (Sweden)

    Bruce Clarke

    2014-09-01

    Full Text Available In this essay I develop a systems-theoretical observation of John Lilly’s cybernetics of communication in his 1967 work The Mind of the Dolphin. The eight-year-old project that The Mind of the Dolphin recounts for public consumption details his aspiration to achieve an unprecedented breakthrough beyond companionate communion to fully abstract linguistic communication across species boundaries. Between 1959 and 1968 Lilly wagered and lost his mainstream scientific career largely over this audacious, ultimately inconclusive bid to establish and document for scientific validation “communication with a nonhuman mind.” In that effort, however, he mobilized the best available tools, a cutting-edge array of cybernetic concepts. He leaned heavily on the information theory bound up with first-order cybernetics and operated with heuristic computational metaphors alongside the actual computers of his era. As I will elicit through some close readings of his texts, in that process Lilly also homed in on crucial epistemological renovations with a constructivist redescription of cognition that may have influenced and motivated his colleague Heinz von Foerster’s more renowned formulations, arriving in the early 1970s, of a second-order cybernetics.

  2. Kauha : [luuletused] / Pjotr Zahharov ; udmurdi keelest tõlkinud soome keelde Viktor Shibanov, Hannu Oittinen, võru keelde tõlkinud Irina Orehhova, Kauksi Ülle, eesti keelde tõlkinud Taive Särg

    Index Scriptorium Estoniae

    Zahharov, Pjotr

    2005-01-01

    Sisu: Kauha / udmurdi keelest tõlkinud soome keelde Viktor Shibanov, Hannu Oittinen ; Kopsik / udmurdi keelest tõlkinud võru keelde Irina Orehhova, Kauksi Ülle ; Pu-pu : seitse pühendust rähnile 1, 3, 4, 4, 5-7 / udmurdi keelest tõlkinud eesti keelde Irina Orehhova, Taive Särg ; Metamorfoosid 3-8 / udmurdi keelest tõlkinud eesti keelde Irina Orehhova, Taive Särg

  3. VizieR Online Data Catalog: The Canada-France Redshift Survey (CFRS) (Lilly+, 1995)

    Science.gov (United States)

    Lilly, S. J.; Le Fevre, O.; Crampton, D.; Hammer, F.; Tresse, L.

    2001-11-01

    The Canada-France Redshift Survey (CFRS) is a collaboration between astronomers in Canada and France: Simon Lilly (University of Toronto), Olivier Le Fevre and Francois Hammer (Observatoire de Paris Meudon), David Crampton (Dominion Astrophysical Observatory, Victoria), Laurence Tresse (Cambridge University), and David Schade and Dan Hudon (University of Toronto). The survey is based primarily on observations with the 3.6m Canada-France-Hawaii Telescope (CFHT) on Mauna Kea, Hawaii. The CFRS consists of spectra of over 1000 faint objects selected to have 17.5 study of normal galaxies at redshifts z > 0.5, corresponding to look-back times of greater than 50% of the age of the Universe. Observations of CFRS galaxies have also been made with the Hubble Space Telescope and the survey will form the basis of future studies with a number of other ground-based and space facilities. We have written a lay-persons guide to the CFRS and the main scientific results that are emerging from it. (1 data file).

  4. MAAGs (Medical Audit Advisory Groups): the Eli Lilly National Clinical Audit Centre.

    Science.gov (United States)

    Baker, R; Fraser, R

    1993-01-01

    Outlines the framework for promoting audit in general practice, created as one part of the health service reforms. Medical Audit Advisory Groups (MAAGs) were set up in each district with the aim of participation in audit of all general practitioners by April 1992. The activities undertaken have included those recommended by the Department of Health; the most significant of these being the appointment of lay facilitators who are able to assist general practitioners and primary care teams co-operate over efforts to improve the quality of care, and may offer one means of introducing some of the methods of total quality management into general practice. Discusses the problems which remain: audit is not yet sufficiently systematic, interface audit with secondary care is at a very early stage, the ways to involve managers and patients in audit remain to be clarified, and there is little evidence of the consequences of audit in terms of improved care. The Eli Lilly National Clinical Audit Centre has been set up within the Department of General Practice, University of Leicester, in order to address these issues.

  5. Viimeinen tarina Neptunista / Hannu Ollikainen

    Index Scriptorium Estoniae

    Ollikainen, Hannu

    2000-01-01

    Nüüdsest Silja nime kandva Silja Line'i operaatorfirma Neptun Maritime probleemid parvlaeva SuperSeaCat meremeeste palkadega ning kasumit tootnud tax-free kaubanduse lõpetamisega. Tabel: ettevõtte majandusnäitajad 1996-1999. Laevakompanii Neptun Maritime. Laevakompanii Silja

  6. Marss, asfaldilt maha! / Hannu Ahonen

    Index Scriptorium Estoniae

    Ahonen, Hannu

    2010-01-01

    TM võrdleb suuri ja kalleid maastureid: Jeep Grand Cherokee 3,0 CRD TDSL V6; Land Rover Discovery 4 3,0 TDV6 HSE; Mercedes-Benz ML 350 4Matic BlueTEC Off-road Pro; Mitsubishi Pajero 3,2 DID Intense; Toyota Land Cruiser 3,0 D-4D Executive

  7. Autobiograafia kui „tõe” diskursus: Lilli Suburgi „Minu saatusega võitluskäik”. Autobiography as the Discourse of “Truth”: Lilli Suburg’s Minu saatusega võitluskäik

    Directory of Open Access Journals (Sweden)

    Eve Annuk

    2012-04-01

    Full Text Available Lilli Suburg (1841-1923 is an author in Estonian literary and cultural history who is not well researched, though her literary output is sufficiently large and her manuscript heritage many-sided, casting light on the little known aspects of her work and activity. Suburg was active in very different fields: she is known as a writer, journalist, feminist and educator. Her literary work is diverse and prolific; she wrote short stories, children’s stories, journalistic texts as well as philosophical essays. In Suburg’s work the autobiographical element plays a significant role, so that we can say that throughout her whole life she wrote her own autobiography, albeit using different forms. In this article, I example specifically the autobiography written by Lilli Suburg (1841-1923 entitled Minu saatusega võitluskäik (My Fight is my Destiny (1914, with the aim of introducing the text to the modern reader and analysing its content and peculiarities. As the text was published almost a hundred years ago, it deserves to be read anew and given a fresh interpretation from a modern point of view. The text certainly adds some new aspects to understanding Lilli Suburg’s life and activity; in the article I will analyse how Suburg looks at herself and her life and the reasons why she chose to write an autobiography with a feminist emphasis. The autobiography was published in the magazine Naiste Töö ja Elu (Women’s Work and Life in 1914 and to date it is the first and only feminist autobiography in Estonia. As Suburg had been a contributor to the magazine since its foundation in 1911, it provided a forum where she was able to share her feminist ideas and worldview with the readers. The magazine’s readers were understanding and supportive of feminist ideas, and the magazine’s focus was on women’s issues and women’s interests, the contributors being the leading women of the time. In her autobiography Suburg gives an overview of her life

  8. Tõlkeloo arvukad dimensioonid / Hannu K. Riikonen

    Index Scriptorium Estoniae

    Riikonen, Hannu K.

    2012-01-01

    Arvustus: Antonie Chalvin, Anne Lange, Daniele Monticelli (Eds.) Between cultures and texts : itineraries in translation history = Entre les cultures et les textes : itinéraires en histoire de la traduction. Frankfurt am Main-Berlin-Bern-Bruxelles-New York-Oxford-Wien 2011

  9. Plasma levels of d1-3-(1,1-dimethylheptyl)-6,6aβ,7,8,10,10aα-hexahydro-1-hydroxy-6,6-dimethyl-9H-dibenzo[b,d]pyran-9-one (Lilly 109514) by quantitative mass fragmentography

    International Nuclear Information System (INIS)

    Sullivan, H.R.; Kau, D.L.K.; Wood, P.G.

    1975-01-01

    Lilly compound 109514 produces alterations in behavioral parameters in laboratory animals. Its relaxant and sedative properties are being studied clinically. A quantitative mass fragmentography (QMF) method for Lilly 109514 has been developed which is sensitive to 2 pmoles/4 ml sample. A similar assay has been developed for the major metabolite (formed by reduction of the 9-keto group). Both assays use deuterium labeled internal standards. Plasma concentrations of the parent drug and the metabolite were determined in dogs following oral administration of single and multiple 400 μg/kg doses of Lilly 109514. Results indicated the drug to be rapidly absorbed and metabolized in this species. Concentrations of the metabolite were significantly higher than those of the parent drug. These results implied that multiple-dosing of Lilly 109514 did not cause induction of metabolizing enzymes or other alterations of the metabolic process in the dog. Determination of the plasma concentrations of the parent drug and metabolite following i.v. administration have permitted the calculation of bioavailability and absorption data. The ability to follow plasma levels for 48 hours after a single i.v. administration of 100 μg/kg of 109514 graphically illustrates the value of quantitative mass fragmentography in kinetic studies of cannabinoids

  10. Väitekiri Balkani ja Baltimaade keelte evidentsiaalsusest / Hannu Tommola

    Index Scriptorium Estoniae

    Tommola, Hannu

    2010-01-01

    Arvustus: Kehayov, Petar. An areal-typological perspective to evidentiality: the cases of the Balkan and Baltic linguistic areas. Tartu : Tartu University Press, 2008. (Dissertationes linguisticae Universitatis Tartuensis ; 10)

  11. Moondunud tõde? / Hannu Ahonen, Velimatti Honkanen, Tapio Koisaari

    Index Scriptorium Estoniae

    Ahonen, Hannu

    2012-01-01

    Testis kümne auto tegelikud CO₂-näidud. Bensiiniautod: Audi A5 Coupé 1,8 TFSI ; BMW 116i ; Citroën C1 1,0i ; Dacia Sandero 1,6 Hi-Flex ; Toyota Verso-S. Diiselautod: Fiat Punto 1,3 M-Jet ; Ford Mondeo 1,6 TDCi ECOnetic ; Opel Insignia Sports Tourer 2,0 CDTI EcoFlex ; Škoda Octavia HB 1,6 TDI GreenLine ; Volvo V70 1,6D DRIVe

  12. Lillie Martin in Gottingen. Lillie Martin, Outstanding Scholar and Teacher: A Centennial Symposium.

    Science.gov (United States)

    Adler, Helmut E.

    This article reports on a symposium commemorating Lillien Martin's dissertation, "Analysis of Difference Sensations," by published in 1899. The symposium marked the centenary celebration in acknowledgement of Martin's pioneer efforts for women in the field of psychology. Psychophysics was concerned with the quantitative assessment of…

  13. Chief of staff finance | Lillie | Scientia Militaria: South African Journal ...

    African Journals Online (AJOL)

    Scientia Militaria: South African Journal of Military Studies. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 12, No 2 (1982) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Chief of staff finance. Ashley C ...

  14. On aeg, mil vajame enam leiba kui lilli / Ants Juske

    Index Scriptorium Estoniae

    Juske, Ants, 1956-2016

    2009-01-01

    Marge Monko isikunäitus "Leib ja lilled" Tallinnas Draakoni Galeriis 21. märtsini. Eksponeeritud fotod ja video "Nora õed". Kunstnik on majanduses ja tööhõives asetleidvaid muutusi uurides aluseks võtnud Narva Kreenholmi Manufaktuuri näited

  15. Longevidade de inflorescências de lírio, de diferentes estádios de colheita, pré-tratadas com sacarose e tiossulfato de prata (STS Longevity of lilly inflorescences harvested at different stages of development and pulsed with sucrose and silver thiosulfate (STS

    Directory of Open Access Journals (Sweden)

    José Geraldo Barbosa

    2006-02-01

    flowers at different ages. They were evaluated at length and opening of the buds, relative water content, content of chlorophyll and longevity. The longevity of lilly flowers variety Ace is influenced by the stage of harvest, with longer longevity for the younger stage, A. Inflorescences harvested at stage A and pulsed with STS had bigger diameter, but the treatment reduced the bud opening and flower quality. The sucrose improved the opening of buds harvested at stage A and increased the flower vase life. Thus the use of sucrose at 5% allowed harvesting the inflorescences at earlier stage, increasing the flower vase life.

  16. Sixpack diisleid / Hannu Ahonen, Pekka Aromaa, Jari Pitkäjärvi, Isak Kullman

    Index Scriptorium Estoniae

    2008-01-01

    Diiselmootoriga mahukad pereautod: Citroën C5 2,0 Hdi Aut.; Ford Mondeo 2,0 TDCi Trend; Mazda 6 Sedan 2,0 TD Elegance; Renault Laguna 2,0 dCi Dynamique; Toyota Avensis 2,0 dt Linea Sol; Volkswagen Passat Sedan 2,0 TDI

  17. Mõõdukad ent ruumikad : [Detroidi autonäitus NAIAS 2012] / Hannu Ahonen

    Index Scriptorium Estoniae

    Ahonen, Hannu

    2012-01-01

    TM võrdleb universaale: Ford Focus 1,6L Wagon Trend; Kia Cee’d SW 1,6; Opel Astra Sports Tourer 1,4 Enjoy; Peugeot 308 SW Active VTi 120; Renault Mègane Grandtour 1,4 Dynamique; Volkswagen Golf Variant 1,2 TSI

  18. Sõjas saavad alati valed mehed surma / Hannu Salonen ; intervjueerinud Margit Tõnson

    Index Scriptorium Estoniae

    Salonen, Hannu, 1972-

    2009-01-01

    Režissöör oma uuest mängufilmist "Vasha" (endine tööpealkiri "Kid ja Killer"), Eesti, Soome, Saksamaa ja Iirimaa koostööfilm, kus kesksetes osades on eestlastest Mart Müürisepp, Rein Oja, Jan Uuspõld jt

  19. [Setomaa. Traditsioonilise arhitektuuri põhijooni ; Setomaa. Unique and genuine] / Hannu Oittinen

    Index Scriptorium Estoniae

    Oittinen, Hannu, 1959-

    2015-01-01

    Tutvustus: Setomaa : traditsioonilise arhitektuuri põhijooni / [tekst: MTÜ Vanaajamaja ja Ahto Raudoja. [Värska] : [Seto Instituut], 2014 ; Setomaa : unique and genuine / SA Seto Instituut ; Paul Hagu jt. [Värska] : Seto Instituut, 2014

  20. Esimene valik / Jaakko Valkiainen, Hannu Häyhä, Sampo Korhonen... [jt.

    Index Scriptorium Estoniae

    Valkiainen, Jaakko

    2014-01-01

    Seitse erineva stiili ja suurusega tsiklit algaja mootorratturi jaoks: BMW F 700 GS, Harley-Davidson XL 883 N Iron, Honda CBR 500 R, Kawasaki Ninja 300, KTM Duke 390, Suzuki GW 250 Inazuma, Yamaha FZ8-S

  1. Salonen: kõik tšetšeenid juba ootavad seda filmi / Hannu Salonen ; intervjueerinud Tiiu Laks

    Index Scriptorium Estoniae

    Salonen, Hannu, 1972-

    2009-01-01

    Režissöör oma uuest mängufilmist "Vasha" (endine tööpealkiri "Kid ja Killer"), Eesti, Soome, Saksamaa ja Iirimaa koostööfilm, kus kesksetes osades on eestlastest Mart Müürisepp, Rein Oja, Jan Uuspõld jt

  2. Via Baltica : Eesti tee Hansaliidust Euroopa Liitu? = Via Baltica : Viron tie Hansaliitosta Euroopan Unioniin? / Hannu Eerikäinen

    Index Scriptorium Estoniae

    Eerikäinen, Hannu

    2004-01-01

    Via Baltica moodustab Läänemere regioonis tähtsaima arengutelje, mis avab Põhja-Euroopale tee EL-ist väljaspool olevatesse riikidesse. Tallinnast saab taas tähtis vahendaja Põhja- ja Kesk-Euroopa vahel

  3. V zamke otkrõlas võstavka fotografi prirodõ Finljandii

    Index Scriptorium Estoniae

    2008-01-01

    Soome loodusfotode näitus "Frozen Horizon" Narva linnuses. Oma töid näitavad Oulu läänis tegutsevad loodusfotograafid Kalervo Ojutkangas, Jorma Luhta, Hannu Hautala, Tauno Kohonen ja Hannu Huttu. Fotograafidest

  4. [J. Tapio. Suljetut vaunut, eli, Kadonnutta aikaa etsimässä ; Jukka Kostiainen. Kinnises tõllas, ehk, Kadunud aega otsimas ; Tatu Vaaskivi. Maarjamaa] / Hannu Oittinen

    Index Scriptorium Estoniae

    Oittinen, Hannu, 1959-

    2013-01-01

    Arvustus: Tapio, J. Suljetut vaunut, eli, Kadonnutta aikaa etsimässä. Porvoo : J. Kostiainen, 2012 ; Kostiainen, Jukka. Kinnises tõllas, ehk, Kadunud aega otsimas / tõlkinud Ants Paikre. Tartu : Atlex, 2013 ; Vaaskivi, Tatu. Maarjamaa / tõlkinud Ants Paikre. Tallinn : Kultuurileht, 2013. (Loomingu raamatukogu)

  5. Estonia halts expansion of "expensive" windmills / Kairi Kurm

    Index Scriptorium Estoniae

    Kurm, Kairi

    2005-01-01

    Majandus- ja kommunikatsiooniministeeriumi osakonnajuhataja Einari Kisel ja AS-i Tuulepargid tegevdirektor Hannu Lamp tuuleenergia tootmisest Eestis. Tabelid: Iga-aastane tuuleenergia tootmine Euroopa Liidus; Planeeritud tuuleenergia tootmine

  6. Keegi ei tea mu nime : [luuletused] / Veiko Märka

    Index Scriptorium Estoniae

    Märka, Veiko, 1964-

    2002-01-01

    Tõlgitud Veiko Märka luulekogust "Tühja aju korinad". Sisu: Keegi ei tea mu nime = Kukaan ei tiedä mun nimee ; "Kui ma kuulen sõnu..." = "Kun kuulen ilmauksen..." ; "Esimese..." = "Ensimmäisenä..." ; "Igal hommikul..." = "Joka aamu..." / tlk. Hannu Oittinen. Väike perenaine = Pikku perheenäiti / tlk. Hannu Oittinen ja Tuglas-seuran kääntäjäpiiri. Progressi triumf : (Poeem) = Kehityksen voitto : (Runoelma) / tlk. Hannu Oittinen. Minimalistlikud muinasjutud = Minimalistisia satuja / tlk. Heli Laaksonen ja Hannu Oittinen. Kõige turvalisem seks = Turvallisinta seksiä ; Abistame Aafrikat! = Autetaan Afrikkaa! ; "Taome..." = "Taotaan..." ; "Edasi..." = "Eteenpäin..." ; "Isegi juhus..." = "Edes sattuma..." ; "Miinus ja miinus..." = "Miinus ja miinus..." / tlk. Hannu Oittinen. Leijonien pakottaja ; Kotka ja Vaasa: Ystävyyskaupunkit

  7. [Uue Eesti loojad. Uuden Viron luojat : välähdyksiä Tampereen Rudolf Steiner-koulun viro-kummiryhmän toiminnasta 1989-1999 ; Varsinais-Suomi ja Viro : Varsinais-Suomen Virokeskus 20 vuotta] / Hannu Oittinen

    Index Scriptorium Estoniae

    Oittinen, Hannu, 1959-

    2015-01-01

    Arvustus: Uue Eesti loojad. Uuden Viron loojat / toimetaja Liisa Niinikangas. Jyväskylä : Lighthouse Consulting, 2014 ; Varsinais-Suomi ja Viro : Varsinais-Suomen Virokeskus 20 vuotta / toimetajad Veikko Laakso ja Kirsi Äyräs. [Turku] : Varsinais-Suomen Viro-keskus, 2015

  8. 77 FR 31722 - New Animal Drugs; Change of Sponsor; Estradiol; Estradiol Benzoate and Testosterone Propionate...

    Science.gov (United States)

    2012-05-30

    ..., Division of Eli Lilly & Co. DATES: This rule is effective May 30, 2012. FOR FURTHER INFORMATION CONTACT... this table to Elanco Animal Health, Division of Eli Lilly & Co., Lilly Corporate Center, Indianapolis...

  9. Liina Tennosaar : "Enda meelest olen ilus vanainimene" / Liina Tennosaar ; interv. Jaanus Kulli

    Index Scriptorium Estoniae

    Tennosaar, Liina

    2008-01-01

    Näitlejanna endast ja osalemisest Hannu Saloneni käe all valmivas Eesti-Soome-Saksamaa koostööfilmis "Kid & Killer". Lisaks "Epp Pillarpart andis Liina lapsele nime" ja meenutus "Teismeline soovis surmapurjekal seilata"

  10. Lugemisnoppeid / Toomas Tiivel

    Index Scriptorium Estoniae

    Tiivel, Toomas, 1952-

    2012-01-01

    Tutvustus: Tarand, Andres, Strandberg, Marek. Rahvusliku julgeoleku küsimus : Andres Tarandi ja Marek Strandbergi kriitilised kõned Eesti energeetika arengu asjus. Tallinn, 2010 ; Lauerma, Hannu. Usk, lootus ja ohtlik bluff : julgustamisest vaimse terrorini. Tallinn, 2008

  11. Raamatureisid Veneetsiasse / Margus Haav

    Index Scriptorium Estoniae

    Haav, Margus, 1969-

    2005-01-01

    Arvustus: Girardi, Robert. Vaporetto 13 / ingl. k. tlk. Karin Suursalu. Tallinn : Kultuurileht, 2005. (Loomingu Raamatukogu) ; Raittila, Hannu. Canal Grande : [romaan] / tõlkinud Aivo Lõhmus. Tallinn : Varrak, 2003 (Moodne aeg)

  12. Dostojevskilik kapseldunud elu Q-teatris / Andres Laasik

    Index Scriptorium Estoniae

    Laasik, Andres

    1997-01-01

    Fjodor Dostojevski jutustuse 'Ülestähendusi põranda alt' järgi tehtud Soome Q-teatri lavastusest 'Kelder' ("Kellari", dramatiseerinud Antti Hietala, Hannu Kivioja ja Erik Söderblom, lav. Erik Söderblom)

  13. Lahti uus Sibelius-talo

    Index Scriptorium Estoniae

    2000-01-01

    Lahtis avati esimene puulipikuist ehitatud kontserdimaja, mis sai Sibeliuse nime. Arhitektid Hannu Tikka, Kimmo Lintula. Sibelius-talo hea akustika tagamiseks osales firma Artec New Yorgist eesotsas akustik Russell Johnsoniga.

  14. 76 FR 55110 - In the Matter of Certain Gemcitabine and Products Containing Same; Notice of Commission...

    Science.gov (United States)

    2011-09-06

    ..., 2011, based on a complaint filed by Eli Lilly and Company (``Lilly''). 76 FR 16445. The complaint.... (``Hansoh'') as respondents. On August 9, 2011, Lilly, Hospira, and Intas filed a joint motion to terminate... Hansoh filed a response supporting termination, but for different reasons than those advanced by Lilly...

  15. Rauno Pukonen : Meie toodangut armastatakse, meid endid mitte / Rauno Pukonen ; interv. Svea Talving

    Index Scriptorium Estoniae

    Pukonen, Rauno

    2004-01-01

    Farmaatsiafirmast Eli Lilly, ravimifirmade madalast mainest. Eli Lilly filiaali juhi sõnul ei lase väike turg ja tagasihoidlik kompensatsioon võimalikku ravimivalikut Eestisse tuua. Lisa: Fakte ettevõttest

  16. 76 FR 16445 - In the Matter of Certain Gemcitabine and Products Containing Same; Notice of Investigation

    Science.gov (United States)

    2011-03-23

    ... Act of 1930, as amended, 19 U.S.C. 1337, on behalf of Eli Lilly and Company of Indianapolis, Indiana. Eli Lilly filed letters supplementing the complaint on February 9 and 16, 2011. The Commission requested additional information on March 2, 1011. Eli Lilly responded with additional information...

  17. 78 FR 44432 - New Animal Drugs; Change of Sponsor; Fentanyl; Iron Injection

    Science.gov (United States)

    2013-07-24

    ... for an NADA from Nexcyon Pharmaceuticals, Inc. to Elanco Animal Health, A Division of Eli Lilly & Co..., NADA 141-337 for RECUVYRA (fentanyl) Transdermal Solution to Elanco Animal Health, A Division of Eli Lilly & Co., Lilly Corporate Center, [[Page 44433

  18. 75 FR 9333 - Implantation or Injectable Dosage Form New Animal Drugs; Tilmicosin

    Science.gov (United States)

    2010-03-02

    ... (NADA) filed by Elanco Animal Health, A Division of Eli Lilly & Co. The supplemental NADA provides a...: [email protected] . SUPPLEMENTARY INFORMATION: Elanco Animal Health, A Division of Eli Lilly & Co., Lilly Corporate Center, Indianapolis, IN 46285, filed a supplement to NADA 140-929 for MICOTIL...

  19. 77 FR 46612 - New Animal Drugs; Change of Sponsor; Change of Sponsor Address; Azaperone; Miconazole, Polymyxin...

    Science.gov (United States)

    2012-08-06

    ... Pharmaceutica NV, to Elanco Animal Health, a Division of Eli Lilly & Co. FDA is also amending the animal drug..., polymyxin B sulfate, prednisolone acetate) Otic Suspension to Elanco Animal Health, a Division of Eli Lilly & Co., Lilly Corporate Center, Indianapolis, IN 46285. Following these changes of sponsorship, Janssen...

  20. Vasha paugutab püstolit päriselus nagu filmis / Andres Laasik

    Index Scriptorium Estoniae

    Laasik, Andres, 1960-2016

    2009-01-01

    Võrdlus Hannu Saloneni Eesti, Soome, Saksa ja Iiri koostööfilmis "Vasha" toimunu ja tegelike sündmustega tšetšeeni emigrantide hulgas. Tegelik elu on traagilisem ja dünaamilisem kui mängufilmis näidatu

  1. 20 miljoni eest põnevust / Piret Tibbo-Hudgins

    Index Scriptorium Estoniae

    Tibbo-Hudgins, Piret

    2009-01-01

    Produtsent Eesti-Saksa-Soome-Iirimaa koostööfilmist "Vasha", kus osalevad Eesti näitlejad ning filmitegijad Saksamaalt, Soomest ja Iirimaalt. Filmi režissöör on Hannu Salonen, peategelased Mart Müürisepp ja Mehmet Kurtulus

  2. "Vasha" on mitme lõpuga film / Tiiu Laks

    Index Scriptorium Estoniae

    Laks, Tiiu, 1984-

    2009-01-01

    Hannu Saloneni uuest mängufilmist "Vasha" (endine tööpealkiri "Kid ja Killer"), Eesti, Soome, Saksa ja Iiri koostööfilmist, kus kesksetes osades on türklane Mehmet Kurtulus, eestlastest Mart Müürisepp, Rein Oja, Jan Uuspõld jt

  3. Uue mängufilmi võtted / E. K.

    Index Scriptorium Estoniae

    E. K.

    2008-01-01

    Allfilm koos Saksa, Soome ja Iiri partneritega alustas Tallinnas action-mängufilmi "Kid & Killer" võtteid (režissöör Hannu Salonen, stsenaristid Mart Kivastik ja Katrin Laur, operaator Rein Kotov, produtsent Piret Tibbo-Hudgins)

  4. Varem olin ma mänginud kooliteatris vaid puud / Jaanus Kulli

    Index Scriptorium Estoniae

    Kulli, Jaanus, 1955-

    2008-01-01

    Allfilm koos Saksa, Soome ja Iiri partneritega alustas Tallinnas action-mängufilmi "Kid & Killer" võtteid (režissöör ja üks stsenariste Hannu Salonen, stsenaristid Mart Kivastik ja Katrin Laur, operaator Rein Kotov, peaprodutsent Piret Tibbo-Hudgins). Ühte peaossa valiti Westholmi gümnaasiumi õpilane Mart Müürisepp

  5. Viru keskuses plahvatab mitu päeva järjest / Ants Vill

    Index Scriptorium Estoniae

    Vill, Ants, 1955-

    2008-01-01

    Allfilm koos Saksa, Soome ja Iiri partneritega alustas Tallinnas action-mängufilmi "Kid & Killer" võtteid (režissöör Hannu Salonen, stsenaristid Mart Kivastik ja Katrin Laur, operaator Rein Kotov, produtsent Piret Tibbo-Hudgins). 24-25. märtsil filmitakse Viru Keskuses

  6. Viikki kool : Kevätkatu 2, Helsingi = Viikki Teacher Training School

    Index Scriptorium Estoniae

    2004-01-01

    Viiki uus kool toimib Helsingi Ülikooli pedagoogikaosakonna praktikakoolina, siin on nii põhi- kui keskkooliõpe. Raudbetoonelementidest hoone, fassaadid on põhiliselt valged betoonist sandwich-paneelid. Projekteerija: ARK-house Arkkitehdit. Autorid Markku Erholtz, Hannu Huttunen, Jussi Karjalainen. Valmis 2001. 5 välis- ja 7 sisevaadet

  7. Suur müüdikonverents Tartus / Evelin Banhard

    Index Scriptorium Estoniae

    Banhard, Evelin

    2008-01-01

    Tartus toimunud rahvusvahelisest konverentsist "Suurte kultuuriliste ja kirjanduslike müütide saatus tänapäeval". Pikemalt Liisa Saariluoma, Jüri Talveti, Angelika Stefanova, Tanel Lepsoo, Caroline De Wagteri, Sonia Bravo Utrera, Ana Martinoska, Marin Laagi, Rutt Hinrikuse, Jeanne Elisabeth Gleseneri, Sabine Coelsch-Foisneri, Harvey L. Hixi ja Hannu K. Riikoneni ettekannetest

  8. Eesti luule Kajaani sõnakunsti päevadel / Endel Mallene

    Index Scriptorium Estoniae

    Mallene, Endel, 1933-2002

    1996-01-01

    Ülevaade Kajaani sõnakunsti päevadest 'Sõna ja heli' ('Sana ja sävel'), kus toimus ka eesti kirjanike luuleõhtu ja Sass Suumani valikkogu esitlus: Suuman, Sass. Viisaampaa ei ole / Tlk. Pirkko Huurto, Ritva Hyry, Hannu Oittinen. Saarijärvi : Pohjoinen, 1996

  9. Sibeliustalo Lahtis / Märt Martinson

    Index Scriptorium Estoniae

    Martinson, Märt

    2000-01-01

    Märtsis 2000 valminud soome arhitektide Hannu Tikka ja Kinno Lintula projekteeritud Sibeliostalost, mis koosneb kontserdi- ja kongressihoonest, vanast tehasehoonest ja nende vahele jäävast Metsahallist. Kontserdisaali akustika on loodud hoone projekteerijate ja Russell Johnsoni (New York) koostööna. 8 ill

  10. Ravimikontsern võitis soodusravimitülis kohtus sotsiaalministeeriumi / Signe Kalberg

    Index Scriptorium Estoniae

    Kalberg, Signe, 1959-

    2007-01-01

    Tallinna halduskohtu otsusest rahvusvahelise farmaatsiakontserni Eli Lilly ja sotsiaalministeeriumi vahelises kohtuasjas aktiivsus- ja tähelepanuhäiretega lastele mõeldud ravimi soodustuse taotlumise kohta

  11. Long-term efficacy of adalimumab in the treatment of uveitis associated with juvenile idiopathic arthritis

    OpenAIRE

    Kotaniemi, Kaisu; S?il?, Hanna; Kautiainen, Hannu

    2011-01-01

    Kaisu Kotaniemi1,2, Hanna Säilä2, Hannu Kautiainen31Helsinki University Hospital, Helsinki, Finland; 2Orton Orthopaedic Hospital and Rehabilitation Unit, Helsinki, Finland; 3Unit of Primary Health Care, Kuopio University Hospital, Kuopio, FinlandBackground: The purpose of this study was to investigate the long-term effects of adalimumab, a tumor necrosis factor alpha antagonist, in the treatment of uveitis associated with juvenile idiopathic arthritis.Methods: Adalimumab was...

  12. Terrorism, pommid ja pangarööv / Anari Koppel

    Index Scriptorium Estoniae

    Koppel, Anari

    2008-01-01

    Töös olevad Eesti mängufilmid - "Kid&Killer" (produtsent Piret Tibbo Hudgins, stsenaristid Mart Kivastik, Katrin Laur ja Hannu Salonen, kes ka filmi lavastab), "Külaline" (soome, saksa eesti, inglise koostööfilm, lavastaja Jukka-Pekka Valkeapää, operaator Tuomo Hutri, produtsent Marit Ahven), "Pangarööv" (režissöör Andrus Tuisk, stsenarist Mihkel Ulman, produtsent Manfred Vainokivi)

  13. Bagatellid : maailm / Nele-Eva Steinfeld, Ivo Heinloo

    Index Scriptorium Estoniae

    Steinfeld, Nele-Eva

    2011-01-01

    Muusikasõnumeid maailmast: Jiri Belohlavek naaseb Tšehhi filharmoonia peadirigendiks. Alfred Brendel 80. Sir Simon Rattle'i debüüt Metropolitan Operas. Soome raadio sümfooniaorkestri peadirigendiks saabHannu Lintu. 2012. aasta Viini uusaastakontserti juhatab Maris Jansons. Uus täht jazzitaevas - Christian Scott. Valik uusi jazziraamatuid. Itaalia muusikaajakiri Musica Jazz valis aasta parimaid jazzmuusikuid. Grammy võitjad selgunud. Michael Jackson jätkab postuumselt müügirekordite purustamist

  14. Neuroscience-Enabled Complex Visual Scene Understanding

    Science.gov (United States)

    2012-04-12

    34, Rivista di Psicologia 49 (1): 7–30 • Kauppinen, Hannu. Seppanen, Tapio and Pietikainen, Matti. An Experimental Comparison of Autoregressive and...a Social Robot,“ IJCAI, pp. 1146-1151, 1999. [63] G. Heidemann, R. Rae, H. Bekel, I. Bax, and H. Ritter, ”Inte- grating Context-free and Context... social interaction. In Interna- tional Conference on Robotics, Automation, and Mecha- tronics (RAM 2006), Bangkok Thailand. Se, S., Lowe, D. G

  15. Atomoxetine Open-Label Trial in ADHD

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2002-07-01

    Full Text Available Atomoxetine (originally named tomoxetine, a new therapy for attention deficit hyperactivity disorder (ADHD marketed by Eli Lilly, was compared to methylphenidate in a prospective, randomized, open-label study for 10 weeks duration, at the University of Nebraska Medical Center, Massachusetts General Hospital, Mount Sinai Medical Center, Carolinas Medical Center, and Lilly Research Laboratories.

  16. Ainult 1%-meestest ei ole erektsioonihäire ravitav

    Index Scriptorium Estoniae

    2004-01-01

    Erektsioonihäirete põhjustest, seotud haigustest ja ravimeetoditest rääkisid ravimifirma Eli Lilly korraldatud loengupäeval uroloog Margus Punab, kardioloog Arvo Rosenthal, psühhiaater Imre Rammul ja Eli Lilly turundusjuht Katrin Lätt

  17. Rauno Pukonen : Turule tulevad vaid oma klassi parimad rohud / Rauno Pukonen ; interv. Vilve Torn

    Index Scriptorium Estoniae

    Pukonen, Rauno

    2006-01-01

    Rahvusvahelise Ravimitootjate Liidu juhatuse esimees ja Eli Lilly Balti regiooni direktor vastab küsimustele, mis puudutavad innovatiivsusest ja kvaliteedist lähtumise põhimõtet ravimitootmises, ravimihindade teket, firma 70 miljoni dollari suurust toetust tuberkuloosiprogrammile, firma tulevikku. Lisad: Eli Lilly & Co 130; Ajalugu

  18. 'Szhigaja eti kulturnõje mostõ...' : Moskva-Tallinn 1958-1986 / Vera Ruber

    Index Scriptorium Estoniae

    Ruber, Vera, 1925-2011

    1997-01-01

    Tööst eesti kirjanduse konsultandina Üleliidulise Kirjanike Liidu juhatusse sekretariaadis. Ka 1959. a. romaanivõistlusel silmapaistnud romaanidest (Lilli Prometi 'Meesteta küla' ja Raimond Kaugveri 'Võõra mõõga teenistuses'), Lilli Prometi romaanist 'Primavera' ja venekeelsest kogumikust 'Eesti noor proosa' (1978)

  19. Health Advocacy Organizations and the Pharmaceutical Industry: An Analysis of Disclosure Practices

    Science.gov (United States)

    Raveis, Victoria H.; Friedman, Anne; Rothman, David J.

    2011-01-01

    Health advocacy organizations (HAOs) are influential stakeholders in health policy. Although their advocacy tends to closely correspond with the pharmaceutical industry's marketing aims, the financial relationships between HAOs and the pharmaceutical industry have rarely been analyzed. We used Eli Lilly and Company's grant registry to examine its grant-giving policies. We also examined HAO Web sites to determine their grant-disclosure patterns. Only 25% of HAOs that received Lilly grants acknowledged Lilly's contributions on their Web sites, and only 10% acknowledged Lilly as a grant event sponsor. No HAO disclosed the exact amount of a Lilly grant. As highly trusted organizations, HAOs should disclose all corporate grants, including the purpose and the amount. Absent this disclosure, legislators, regulators, and the public cannot evaluate possible conflicts of interest or biases in HAO advocacy. PMID:21233424

  20. Developing good scientific publishing practices: one pharmaceutical company's perspective.

    Science.gov (United States)

    Dowsett, Sherie A; Van Campen, Luann E; Bednar, Lisa A

    2010-06-01

    The scientific publishing practices of the pharmaceutical industry have been heavily criticized in recent years due to the inherent conflict of interest that arises when a pharmaceutical company publishes findings around its own drugs. Eli Lilly and Company ('Lilly') strives for transparency in its day-to-day activities, and, here, shares its principles, policies and practices on publishing "Lilly-sponsored" research. A conflict of interest does not necessarily equate to biased presentation of research findings, and operating a successful, for-profit business and maintaining a focus on improving the health of patients are not mutually exclusive goals. There is, however, potential for bias, and it is incumbent upon a for-profit to develop publication principles, policies and practices to address this. To this end, Lilly's Principles of Medical Research states that 'Lilly discloses publicly all medical research results that are important to patients, healthcare providers or payers--whether favorable or unfavorable to a Lilly product--in an accurate, objective, and balanced manner ...' The preparation of publications of Lilly-sponsored research involves close collaboration between external (i.e., academic or otherwise non-industry employees) and Lilly scientific researchers (including scientific writers), with both serving as authors. Lilly does not support 'ghost' or 'guest' authorship. Authorship is not just recognition of contribution but also public acknowledgement of responsibility for content, and all authors are expected to take an active role in developing the manuscript in line with the International Committee of Medical Journal Editors-based authorship requirements. This is agreed to by authors before the manuscript is started. Lilly provides external authors with access to the trial data for manuscript development. Lilly does not pay external authors for their involvement in manuscript development. Scientific writers at Lilly, often with advanced scientific

  1. Korp! Filiae Patriae 85. aastapäeva pidustused Los Angeleses / Lumme Erilt

    Index Scriptorium Estoniae

    Erilt, Lumme

    2005-01-01

    5. novembril 2005 tähistas Filiae Patriae Kalifornia koondis Los Angelese Eesti Majas piduliku õestuspeo ning ühise perekonnaõhtuga koos korp! Rotaliaga aastapäeva. Peeti kõnesid, oli tervitusi, muusikat, palju lilli

  2. Naised mõrvarite jälil / Kaisa Karu

    Index Scriptorium Estoniae

    Karu, Kaisa

    2010-01-01

    Kanal 2 ekraanil kaks naispeaosalistega krimisarja : uurija Lilly Rush (Kathryn Morris) sarjas "Jahtunud jälg" (USA, 2003-... ) ja Brenda Leigh Johnson (Kyra Sedgwick) seriaalis "Vahelevõtja" (USA, 2005-... )

  3. Täiskasvanud õppija nädal 2010 / Reet Saar

    Index Scriptorium Estoniae

    Saar, Reet, 1959-

    2010-01-01

    Raplamaa Aasta õppija on Märjamaa perearstikeskuse õde Ljudmilla Tamp, Aasta koolitaja tantsuõpetaja Lilli Teesalu, Aasta koolitussõbralikum organisatsioon on Kehtna põhikool ja aasta koolitussõbralikum omavalitsus Kohila vald

  4. Presidential Green Chemistry Challenge: 1999 Greener Synthetic Pathways Award

    Science.gov (United States)

    Presidential Green Chemistry Challenge 1999 award winner, Lilly Research Laboratories, developed a low-waste drug synthesis using yeast for a stereospecific reduction, reducing solvent amounts, and replacing chromium oxide.

  5. Effect of monensin on fermentation characteristics of the artificial rumen.

    OpenAIRE

    Wallace, R J; Cheng, K J; Czerkawski, J W

    1980-01-01

    Addition of monensin (Rumensin, Eli Lilly and Co.) to an artificial rumen immediately depressed the digestion of roughage and of roughage/concentrate (50:50) feeds. Methane and propionate production were affected only with the roughage/concentrate feed.

  6. Transition et amélioration des indices mondiaux de philanthropie ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Cette subvention aide à transférer les activités d'élaboration des indices mondiaux de dons privés du Center for Global Prosperity de l'Hudson Institute à la Lilly Family School of Philanthropy de l'Université de l'Indiana. Ce projet vise principalement sur l'inclusion des pays à économie émergente. La Lilly Family School ...

  7. Mõnda Eesti kirjanduselust Moskva vaatevinklist (1958-1986) : [mälestusi ja päevikumärkmeid aastaist 1968-1969] / Vera Ruber

    Index Scriptorium Estoniae

    Ruber, Vera, 1925-2011

    1997-01-01

    Tööst eesti kirjanduse konsultandina Üleliidulise Kirjanike Liidu juhatuse sekretariaadis. Ka 1959. a. romaanivõistlusel silmapaistnud romaanidest (Lilli Prometi "Meesteta küla" ja Raimond Kaugveri "Võõra mõõga teenistuses"), Lilli Prometi romaanist "Primavera" ja venekeelsest kogumikust "Eesti noor proosa" ("Эстонская молодая проза", koost. Endel Mallene ja Rein Saluri, 1978)

  8. IBBY Eesti osakond 2007

    Index Scriptorium Estoniae

    2007-01-01

    IBBY Eesti osakond esitas Astrid Lindgreni mälestusauhinna kandidaatideks kirjanik Aino Perviku, illustraatorid Regina Lukk-Toompere ja Ilon Wiklandi. Paabeli Torni auhinna pälvis Arvo Valton komi kirjaniku Vladimir Timini noorsooromaani "Vana-Permi poisi Tikö seiklused" eesti keelde tõlkimise eest. IBBY aunimekirja esitati A. Kivirähk raamatuga "Leiutajateküla Lotte", kunstnik Jüri Mildeberg illustratsioonidega raamatule "Ruttu tuttu" ja tõlkija Piret Saluri Hannu Mäkela raamatu "Härra Huu teeb aiatööd" tõlkimise eest

  9. Orally disintegrating olanzapine review: effectiveness, patient preference, adherence, and other properties

    Directory of Open Access Journals (Sweden)

    Montgomery W

    2012-02-01

    Full Text Available William Montgomery1, Tamas Treuer2, Jamie Karagianis3, Haya Ascher-Svanum4, Gavan Harrison51Global Health Outcomes, Eli Lilly and Company, Sydney, Australia; 2Emerging Markets Business Unit (Neuroscience, Eli Lilly and Company, Budapest, Hungary; 3Eli Lilly and Company, Indianapolis, IN, USA; 4Global Health Outcomes, Eli Lilly and Company, Indianapolis, IN, USA; 5Asia-Pacific Medical Communications, Eli Lilly and Company, Sydney, AustraliaAbstract: Orally disintegrating olanzapine (ODO is a rapid-dissolving formulation of olanzapine which disintegrates in saliva almost immediately, developed as a convenient and adherence-enhancing alternative to the standard olanzapine-coated tablet (SOT. Clinical studies, which form the basis of this review, have shown ODO and SOT to have similar efficacy and tolerability profiles. However, ODO appears to have a number of advantages over SOT in terms of adherence, patient preference, and reduction in nursing burden. Overall, the existing clinical data suggests that compared to SOT, ODO is not only well-suited for difficult-to-treat, agitated, and/or nonadherent patients but, due to its potential ability to improve adherence and greater patient preference, may also be an appropriate formulation for the majority of patients for which olanzapine is the antipsychotic of choice.Keywords: orodispersible formulation, orally disintegrating, olanzapine, atypical antipsychotics, patient adherence, preference, schizophrenia, bipolar disorder

  10. Proceedings of the 2nd international advisory committee on biomolecular dynamics instrument DNA in MLF at J-PARC

    International Nuclear Information System (INIS)

    Arai, Masatoshi; Aizawa, Kazuya; Nakajima, Kenji; Shibata, Kaoru; Takahashi, Nobuaki

    2009-07-01

    The 2nd International Advisory Committee on the 'Biomolecular Dynamics Backscattering Spectrometer DNA' was held on November 12th - 13th, 2008 at J-PARC Center, Japan Atomic Energy Agency. This IAC has been organized for aiming to realize an innovative neutron backscattering instrument in the Materials and Life Science Experimental Facility (MLF) at the J-PARC and therefore four leading scientists in the field of neutron backscattering instruments has been selected as the member (Dr. Dan Neumann (Chair); Prof. Ferenc Mezei; Dr. Hannu Mutka; Dr. Philip Tregenna-Piggott), and the 1st IAC had been held on February 27th - 29th, 2008. This report includes the executive summary and materials of the presentations in the 2nd IAC. (author)

  11. Proceedings of the international advisory committee on 'biomolecular dynamics instrument DNA' and the workshop on 'biomolecular dynamics backscattering spectrometers'

    International Nuclear Information System (INIS)

    Arai, Masatoshi; Aizawa, Kazuya; Nakajima, Kenji; Shibata, Kaoru; Takahashi, Nobuaki

    2008-08-01

    A workshop entitled 'Biomolecular Dynamics Backscattering Spectrometers' was held on February 27th - 29th, 2008 at J-PARC Center, Japan Atomic Energy Agency. This workshop was planned to be held for aiming to realize an innovative neutron backscattering instrument, namely DNA, in the MLF and thus four leading scientists in the field of neutron backscattering instruments were invited as the International Advisory Committee (IAC member: Dr. Dan Neumann (Chair); Prof. Ferenc Mezei; Dr. Hannu Mutka; Dr. Philip Tregenna-Piggott) for DNA from institutes in the United States, France and Switzerland, where backscattering instruments are in-service. It was therefore held in the form of lecture anterior and then in the form of the committee posterior. This report includes the executive summary of the IAC and materials of the presentations in the IAC and the workshop. (author)

  12. Robert Aymar receives one of the highest Finnish distinctions

    CERN Multimedia

    2008-01-01

    On 9 December 2008 Robert Aymar, CERN Director-General, was awarded the decoration of Commander, first class, of the Order of the Lion of Finland by the President of the Republic of Finland. This decoration, one of the highest of Finland, was presented in a ceremony by the Ambassador Hannu Himanen, Permanent Representative of Finland to the UN and other international organisations in Geneva. Robert Aymar was honoured for his service to CERN, the LHC, his role in the cooperation between Finland and CERN, as well as his contribution to science in general. In his speech the ambassador underlined CERN’s efforts in the field of education, mentioning the High school teachers programme.

  13. Suicidality and aggression during antidepressant treatment

    DEFF Research Database (Denmark)

    Sharma, Tarang; Guski, Louise Schow; Freund, Nanna

    2016-01-01

    reports for duloxetine, fluoxetine, paroxetine, sertraline, and venlafaxine obtained from the European and UK drug regulators, and summary trial reports for duloxetine and fluoxetine from Eli Lilly's website.Eligibility criteria for study selection Double blind placebo controlled trials that contained any...

  14. Collaborative learning in an academic writing workshop

    African Journals Online (AJOL)

    Hennie

    claims that modelling, offering a critique of think- ing out aloud .... Maxwell, 1994) by writing a sentence beginning with 'I want ... because when you talk to people in a language which is ..... workshop as “most successful”, particularly as it .... Baltimore: The John Hopkins ... Coffin C, Curry MJ, Goodman S, Hewings A, Lillis TM.

  15. Harry Potter ja Scarlett käivad kohut / Ilona Martson

    Index Scriptorium Estoniae

    Martson, Ilona, 1970-

    2001-01-01

    Alice Randalli romaan "Tuul on läinud" - samad sündmused kui Margaret Mitchelli romaanis "Tuulest viidud", ainult neegerorjade vaatevinklist. Nancy Stofferi raamatud "Larry Potter ja tema parim sõber Lilly" ja "Legend Rah'ist ja Mugudest" ilmusid 1984. a. Joanne Kathleen Rowlingi "Harry Potter" lood aga valmisid hiljem

  16. Reis kosmosesse : [Floating-kambrist] / Marika Makarova

    Index Scriptorium Estoniae

    Makarova, Marika

    2011-01-01

    Ameerika psühholoogi John C. Lilly poolt kasutusele võetud Floating-kambrist ehk hõljumisvannist, mis aeglustab ajulaineid ning seeläbi aitab vähendada lihaspinget, stressi, ärevust, peavalusid, vererõhku ning parandada und, selgroo- ja kaelavigastusi, suurendada loovust ja heaolu jne

  17. Networked Success and Failure at Hybritech

    Science.gov (United States)

    Jones, Mark Peter

    2011-01-01

    The author presents an historical account of scientific work conducted at a commercial biotech firm in San Diego called Hybritech. It tells of disruptions in research programs following the acquisition of the company by the pharmaceutical giant Eli Lilly in 1986. The story centers on responses to an organizational challenge that research managers…

  18. Résultats de recherche | Page 29 | CRDI - Centre de recherches ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Transition et amélioration des indices mondiaux de philanthropie. Cette subvention aide à transférer les activités d'élaboration des indices mondiaux de dons privés du Center for Global Prosperity de l'Hudson Institute à la Lilly Family School of Philanthropy de l'Université de l'Indiana.

  19. Résultats de recherche | Page 41 | CRDI - Centre de recherches ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Transition et amélioration des indices mondiaux de philanthropie. Cette subvention aide à transférer les activités d'élaboration des indices mondiaux de dons privés du Center for Global Prosperity de l'Hudson Institute à la Lilly Family School of Philanthropy de l'Université de l'Indiana. Projet.

  20. Résultats de recherche | Page 40 | CRDI - Centre de recherches ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Transition et amélioration des indices mondiaux de philanthropie. Cette subvention aide à transférer les activités d'élaboration des indices mondiaux de dons privés du Center for Global Prosperity de l'Hudson Institute à la Lilly Family School of Philanthropy de l'Université de l'Indiana. Projet.

  1. Эксклюзивный catwalk в квартале Baltika

    Index Scriptorium Estoniae

    2010-01-01

    9. septembril näidati Baltika kvartalis loomeettevõtlusega tegelejatele välismaalt eesti noorte disainerite eksklusiivset moeetendust "Creative Incubator Fashion Show". Osalejateks Maki, Uma, Donkey Hot, Kalle Aasamäe ja Lilli Jahiloo. Show toimus rahvusvahelise moetegijate kokkutuleku raames, Loomeinkubaatori margi all

  2. Neljakümnes kevad : [luuletused] / Niina Obrezkova ; tlk. Arvo Valton

    Index Scriptorium Estoniae

    Obrezkova, Niina, 1965-

    2006-01-01

    Sisu: Neljakümnes kevad ; "Oleme kõik lapsed..." ; "Hommikvestlust pidada on hilja..." ; "Kingi mulle lilli sa..." ; "On mehi..." ; "Mälu mulle uksed avas ise..." ; "Kolm on valu südames..." ; "Helge pisar..." ; "Ei salahoovusi mus leidu..." "Miskitviisi...". Luuletused paralleelselt komi ja eesti keeles

  3. 77 FR 28761 - Mother's Day, 2012

    Science.gov (United States)

    2012-05-16

    ... House Council on Women and Girls as one of my first acts in office--to ensure we integrate the needs of women and girls into every decision we make. I was proud to sign the Lilly Ledbetter Fair Pay Act, which continues to help women secure equal pay for equal work, and my Administration continues to promote...

  4. Turbulent Convection in an Anelastic Rotating Sphere: A Model for the Circulation on the Giant Planets

    Science.gov (United States)

    2008-06-01

    Raffaele Ferrari, Adam Showman, Dick Lindzen, Baylor Fox-Keiper, Jonathan Lilly, Tapio Schneider, Carl Wunsch and Bill Hubbard. Particularly I thank Jean...Cuzzi, J., Pollack, J. B.. Danielson, G. E., Ingersoll, A., Davies, M. E., Hunt, G. E., Morrison, D., Owen, T.. Sagan , C., Veverka, J., Strom, R

  5. Veel üks fond õpetajate toetuseks

    Index Scriptorium Estoniae

    2002-01-01

    Inna Mathiesen annetas sihtasutusele Eesti Rahvuskultuuri Fond oma vanemate mälestuse jäädvustamiseks 300 000 krooni, millega pandi alus Lilly ja Hugo Pärnamäe Fondile. Sellega tahetakse toetada pedagooge, kes on koolis töötanud vähemalt kaks aastat

  6. Drug Advertising and the FDA.

    Science.gov (United States)

    Levesque, Cynthia

    With increases in consumer focused advertising for prescription drugs, the Federal Drug Administration has renewed efforts to protect the public from false advertising. In 1982, it charged that the press kits Eli Lilly and Company distributed to reporters on its new antiarthritis drug, Oraflex, misrepresented the product. It recommended that Lilly…

  7. Pildid räägivad lugusid, vorstid samuti / Andry Ervald

    Index Scriptorium Estoniae

    Ervald, Andry

    2006-01-01

    Koomiksinäitus Rakvere galeriis. Osa võtavad Peeter Krosmann (1971), Kristel Maamägi (1986), Lilli-Krõõt Repnau (1982), Elina Sildre (1980), Joonas Sildre (1980), Veiko Tammjärv (1967), Paco Ulman (1980), Edvin Aedma ja rühmitus Endorfin Fractured Communications. Kristel Maamägi oma töödest

  8. A Long Island Consortium Takes Shape. Occasional Paper No. 76-1.

    Science.gov (United States)

    Taylor, William R.

    This occasional paper, the first in a "new" series, describes the background, activities, and experiences of the Long Island Consortium, a cooperative effort of two-year and four-year colleges committed to organizing a model program of faculty development. The consortium was organized under an initial grant from the Lilly Endowment. In May and…

  9. Hydrocarbon source rock potential evaluation of the Late Paleocene ...

    Indian Academy of Sciences (India)

    63

    research is available on its source rock potential evaluation at Nammal Gorge Section in the Salt. Range, Potwar Basin .... methods of Tucker (2003) and Assaad (2008) have been followed. A total of fifteen ..... Business Media. Baker D M, Lillie ...

  10. 76 FR 16643 - NASA Advisory Council; Aeronautics Committee; Meeting

    Science.gov (United States)

    2011-03-24

    ... NATIONAL AERONAUTICS AND SPACE ADMINISTRATION [Notice (11-024)] NASA Advisory Council; Aeronautics... Aeronautics and Space Administration announces a meeting of the Aeronautics Committee of the NASA Advisory.... ADDRESSES: Thursday, April 14, 2011--NASA Dryden Flight Research Center (DFRC), Lilly Drive Building 4825...

  11. Factors affecting treatment adherence to atomoxetine in ADHD: a systematic review

    Directory of Open Access Journals (Sweden)

    Treuer T

    2016-05-01

    Full Text Available Tamás Treuer,1 Luis Méndez,2 William Montgomery,3 Shenghu Wu4 1Neuroscience Research, Eli Lilly and Company, Budapest, Hungary; 2Eli Lilly de Mexico, Mexico City, Mexico; 3Global Patient Outcomes and Real World Evidence, Eli Lilly Australia Pty Ltd, West Ryde, NSW, Australia; 4Neuroscience Research, Eli Lilly Asia, Inc, Shanghai, People’s Republic of China Abstract: The purpose of this paper was to systematically review the literature related to research about the factors affecting treatment adherence and discontinuation of atomoxetine in pediatric, adolescent, and adult patients with attention-deficit/hyperactivity disorder (ADHD. Medline was systematically searched using the following prespecified terms: “ADHD”, “Adherence”, “Compliance”, “Discontinuation”, and “Atomoxetine”. We identified 31 articles that met all inclusion and exclusion criteria. The findings from this review indicate that persistence and adherence to atomoxetine treatment were generally high. Factors found to influence adherence and nonadherence to atomoxetine treatment in ADHD in this review include age, sex, the definition of response used, length of treatment, initial dose of treatment, comorbid conditions, and reimbursement. Tolerability was cited as an important reason for treatment discontinuation. More research is needed to understand those factors that can help to identify patients at risk for poor adherence and interventions that could improve treatment adherence early in the stage of this illness to secure a better long-term prognosis. Keywords: atomoxetine, treatment discontinuation, adherence, compliance, ADHD medication, relapse

  12. Moeloojad võtavad modelliks unarusse jäetud inimesi / Anneli Aasmäe

    Index Scriptorium Estoniae

    Aasmäe, Anneli, 1973-

    2011-01-01

    Eesti Kunstiakadeemia ja Turu Novia ülikooli ühisprojektist "Fashion Empowerment", mille raames kavatsevad tudengid pühenduda mingile spetsiifilise vajadusega inimgrupile sobivate riiete ja jalatsite tegemisele. Projekti juhib moedisainer Lilli Jahilo. Ratastoolikasutajatele hakkab jalatseid disainima nahakunsti eriala tudeng Mari Maripuu

  13. Sügisene moevaatemäng / Britt Rosen

    Index Scriptorium Estoniae

    Rosen, Britt, 1968-

    2008-01-01

    FIBITi moepäevad Viru keskuses, korraldaja Anu Kikas. Arne Niidu, Anu Samarüütel-Longi, Tanel Veenre kollektsioonidest. Kalle Aasamäe, Lilli Jahilo, Aet Alevi, Anu Samarüütel-Longi ja Tanel Veenre kommentaarid

  14. Külanäitemäng üllatas tenori ja kooriga / Liisi Seil

    Index Scriptorium Estoniae

    Seil, Liisi, 1971-

    2009-01-01

    17.-19. juulini toimus Lilli külas 4. Nava lava festival. Loeti luulet ja mängiti Jaak Kõdari kirjutatud mulgikeelset näitemängu "Kõik läheb mööda" ning lasteetendust "Hundi ja Rebase lend lõunanabale". Mõlemad lavastas Silvia Soro

  15. Piiriäärne lava valmistub taas esietenduseks / Margus Haav

    Index Scriptorium Estoniae

    Haav, Margus, 1969-

    2008-01-01

    Lõuna-Eestis Lilli külas algaval Nava lava festivalil tuuakse publiku ette Nava talu peremehe Jaak Kõdari näidend "Jukra", lavastaja Silvia Soro. Üht kandvat rolli mängib näitleja Lembit Eelmäe

  16. Humalog Mix25 improves 24-hour plasma glucose profiles ...

    African Journals Online (AJOL)

    Most patients with type 2 diabetes mellitus (T2DM) administer insulin twice daily, yet many use premixed insulin preparations (Lilly, data on file). Premixtures of short- or rapid- acting and intermediate-acting insulins twice daily are commonly used, offering convenience and increased dosing accuracy compared with insulins ...

  17. 78 FR 70581 - Notice of Determinations Regarding Eligibility To Apply for Worker Adjustment Assistance

    Science.gov (United States)

    2013-11-26

    ... Eli Lilly & Company, South Pharmaceutical Sales Indianapolis, Representatives, Throughout the IN... identified by name by the International Trade Commission as a member of a domestic industry in an..., etc. 83,080 HSBC Bank USA, N.A., HSBC USA, Buffalo, NY...... September 12, 2012. HSBC North America...

  18. Habent sua fata motae picturae / Jaan Ruus

    Index Scriptorium Estoniae

    Ruus, Jaan, 1938-2017

    2008-01-01

    1968. aastal Eesti Telefilmis valminud 3-osaline mängufilm "Pimedad aknad" Lilli Prometi jutustuse "Pimedate akende aegu" järgi (režissöör Tõnis Kask) restaureeriti ja helindati uuesti (restaureerisid ETV ja OÜ Profilm). Lisatud "1965-1974: Eesti televisioon õitseb" - olulist ETVs neil aastail

  19. Translational medicine and drug discovery

    National Research Council Canada - National Science Library

    Littman, Bruce H; Krishna, Rajesh

    2011-01-01

    ..., and examples of their application to real-life drug discovery and development. The latest thinking is presented by researchers from many of the world's leading pharmaceutical companies, including Pfizer, Merck, Eli Lilly, Abbott, and Novartis, as well as from academic institutions and public- private partnerships that support translational research...

  20. Maalitud majad Zalipies / Marje Tammert

    Index Scriptorium Estoniae

    Tammert, Marje

    2003-01-01

    Poola Zalipie külas on elumajad ja kõrvalhooned dekoreeritud erksavärviliste lillebukettidega. Lilli ja linde näeb aknaluukidel, aiapostidel, kaevudel, käimlatel jm. Küla muuseumis on lilledega kaetud kogu interjöör, kapid, nõud ja tikitud tekstiilid. 4 ill

  1. Ramucirumab for Treating Advanced Gastric Cancer or Gastro-Oesophageal Junction Adenocarcinoma Previously Treated with Chemotherapy : An Evidence Review Group Perspective of a NICE Single Technology Appraisal

    NARCIS (Netherlands)

    Büyükkaramikli, N.; H.M. Blommestein (Hedwig); R. Riemsma (Rob); N. Armstrong (Nigel); F.J. Clay (Fiona); J. Ross (Janine); G. Worthy (Gill); J.L. Severens (Hans); J. Kleijnen (Jos); M.J. Al (Maiwenn)

    2017-01-01

    textabstractThe National Institute for Health and Care Excellence (NICE) invited the company that manufactures ramucirumab (Cyramza®, Eli Lilly and Company) to submit evidence of the clinical and cost effectiveness of the drug administered alone (monotherapy) or with paclitaxel (combination therapy)

  2. Similar Efficacy and Safety of Basaglar® and Lantus® in Patients with Type 2 Diabetes in Age Groups (< 65 Years, ≥ 65 Years): A Post Hoc Analysis from the ELEMENT-2 Study.

    Science.gov (United States)

    Pollom, Robyn K; Costigan, Timothy; Lacaya, Lyndon B; Ilag, Liza L; Hollander, Priscilla A

    2018-04-01

    To compare efficacy and safety of Basaglar ® [insulin glargine 100 units/mL; LY insulin glargine (LY IGlar)] to Lantus ® [insulin glargine 100 units/mL; SA insulin glargine (SA IGlar)] in older (≥ 65 years) or younger (Eli Lilly and Company and Boehringer-Ingelheim.

  3. In vitro activity of a new 'higher-Iactam' antibacterial agent LY 193239

    African Journals Online (AJOL)

    1991-03-16

    Mar 16, 1991 ... penicillin. Antimicrobial agents. Solutions of LY 193239 (supplied by Eli Lilly) and tetracycline were freshly prepared in sterile distilled water. Rifampicin was dissolved in dimethyl sul- phoxide and diluted in water. Ampicillin and penicillin were prepared in 0,05M phosphate buffer with final pH 7,0. MICs.

  4. Dulaglutide, a long-acting GLP-1 analog fused with an Fc antibody fragment for the potential treatment of type 2 diabetes

    DEFF Research Database (Denmark)

    Jimenez-Solem, Espen; Rasmussen, Mette H; Christensen, Mikkel

    2010-01-01

    Dulaglutide (LY-2189265) is a novel, long-acting glucagon-like peptide 1 (GLP-1) analog being developed by Eli Lilly for the treatment of type 2 diabetes mellitus (T2DM). Dulaglutide consists of GLP-1(7-37) covalently linked to an Fc fragment of human IgG4, thereby protecting the GLP-1 moiety from...

  5. Clinical utility of orally disintegrating olanzapine in Chinese patients with schizophrenia: a review of effectiveness, patient preference, adherence, and other properties

    Directory of Open Access Journals (Sweden)

    Zhao J

    2014-02-01

    Full Text Available Jingping Zhao,1 Jianjun Ou,1 Haibo Xue,2 Li Liu,2 William Montgomery,3 Tamas Treuer4 1Mental Health Institute of The Second Xiangya Hospital, Hunan Province Technology Institute of Psychiatry, Key Laboratory of Psychiatry and Mental Health of Hunan Province, Central South University, Changsha, Hunan, 2Lilly Suzhou Pharmaceutical Co, Ltd, Jiangsu, People's Republic of China; 3Global Health Outcomes, Eli Lilly and Company, Sydney, Australia; 4Emerging Markets Business Unit (Neuroscience, Eli Lilly and Company, Budapest, Hungary Abstract: The primary objective of this systematic review was to examine the evidence for the efficacy, effectiveness, and safety of orally disintegrating olanzapine in Chinese populations. A systematic literature search was conducted using databases covering international and Chinese journals, ClinicalTrials.gov, and internal and external trial registries at Eli Lilly and Company using search terms related to target countries (People's Republic of China, Hong Kong, and Taiwan and orally disintegrating olanzapine treatment. A publication and one clinical study report were retrieved. The clinical study showed orally disintegrating olanzapine and the standard oral tablet to have similar efficacy and tolerability profiles. A bioequivalence study has shown that orally disintegrating olanzapine and the standard oral tablet have similar pharmacokinetic profiles. Orally disintegrating olanzapine and the standard oral tablet have similar efficacy and tolerability profiles. Keywords: orally disintegrating, olanzapine, Chinese, schizophrenia, patients

  6. Erektsioonihäire põhjustest / Anne Veskimeister

    Index Scriptorium Estoniae

    Veskimeister, Anne, 1960-

    2004-01-01

    Androloog Margus Punab, kardioloog Arvo Rosenthal ja psühholoog Imre Rammul tõid möödunud nädalal toimunud ravimifirma Ely Lilly loengupäeval esile erektsioonihäirete põhjused, seosed teiste haigustega ja ravivõimalused

  7. Grjaznoje proshloje kuklõ Barbi / Igor Silenko

    Index Scriptorium Estoniae

    Silenko, Igor

    2002-01-01

    Nukk Barbie saamislugu - meestele mõeldud seksapiilne saksa nukuke Lilly (autoriks disainer Max Weissbrodt) sai ameerika disaineri Ruth Handleri käe all uue näo ja nime ning debüteeris 1959. a. New Yorgi mänguasjade laadal

  8. Mõtteid raamatust / Koost. Heigi Aaviste

    Index Scriptorium Estoniae

    1995-01-01

    Aut.: Maire Liivamets, Paul Luhtein, Paul-Eerik Rummo, Maksim Gorki, Johannes Semper, R.Descartes, Valmar Adams, Lilli Promet, Paul Rummo, Cicero, Honoré de Balzac, Aleksandr Pushkin, Epikuros, Debora Vaarandi, Arvi Siig, Helene Johani, Juhan Smuul, Friedebert Tuglas

  9. Promotion of Critical Thinking in Clinical Nursing Post Conferences: A Peer Interactive Approach

    Science.gov (United States)

    Stevens, Joanne

    2009-01-01

    Several workshops presented at the 2005 Lilly Conference on College Teaching in Oxford, Ohio, provided the inspiration for redesigning the clinical post conference for a foundational nursing course. Given the complexity and acuity of patient conditions today, fostering critical thinking in student nurses is central to quality patient care. The…

  10. Make love and war ehk ükssarvede ilmumine Tallinnasse = Make love and war, or the unicorns' advent in Tallinn / Rebeka Põldsam

    Index Scriptorium Estoniae

    Põldsam, Rebeka, 1989-

    2012-01-01

    Tallinna linnainstallatsioonide festivali "LIFT11" installatsioonist "Queer-kleepekavihik". Kuraatorid Anna-Stina Treumund ja Jaanus Samma. Autorid Helin Tikerpuu, Katia Weber Piscitelli, Ly Lestberg, Mare Tralla, Ott Pilipenko, Mae Köömnemägi, Andreas Kalkun, Rebeka Põldsam, Lilli-Krõõt Repnau, Aet Kuusik, Jaanus Samma

  11. The Ripple Effect: Lessons from a Research and Teaching Faculty Learning Community

    Science.gov (United States)

    Hershberger, Andrew; Spence, Maria; Cesarini, Paul; Mara, Andrew; Jorissen, Kathleen Topolka; Albrecht, David; Gordon, Jeffrey J.; Lin, Canchu

    2009-01-01

    Building upon a related 2005 panel presentation at the 25th annual Lilly Conference on College Teaching, Miami University, Oxford, Ohio, the authors, several tenure-track assistant professors and tenured associate professors who have participated in a Research and Teaching Faculty Learning Community at Bowling Green State University, share their…

  12. Language Ideology Change over Time: Lessons for Language Policy in the U.S. State of Arizona and Beyond

    Science.gov (United States)

    Fitzsimmons-Doolan, Shannon

    2018-01-01

    In the U.S. state of Arizona, language minority students who are English learners attend schools governed by a restrictive medium of instruction (MOI) language policy (LP). Educators and educational researchers widely agree that effective reforms of this policy are urgently needed (e.g., Arias & Faltis, 2012; Lawton, 2012; Lillie, 2016).…

  13. Clinical development of galunisertib (LY2157299 monohydrate, a small molecule inhibitor of transforming growth factor-beta signaling pathway

    Directory of Open Access Journals (Sweden)

    Herbertz S

    2015-08-01

    Full Text Available Stephan Herbertz,1 J Scott Sawyer,2 Anja J Stauber,2 Ivelina Gueorguieva,3 Kyla E Driscoll,4 Shawn T Estrem,2 Ann L Cleverly,3 Durisala Desaiah,2 Susan C Guba,2 Karim A Benhadji,2 Christopher A Slapak,2 Michael M Lahn21Lilly Deutschland GmbH, Bad Homburg, Germany; 2Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA; 3Lilly Research Laboratories, Eli Lilly and Company, Windlesham, Surrey, UK; 4Lilly Research Laboratories, Eli Lilly and Company, New York, NY, USA Abstract: Transforming growth factor-beta (TGF-β signaling regulates a wide range of biological processes. TGF-β plays an important role in tumorigenesis and contributes to the hallmarks of cancer, including tumor proliferation, invasion and metastasis, inflammation, angiogenesis, and escape of immune surveillance. There are several pharmacological approaches to block TGF-β signaling, such as monoclonal antibodies, vaccines, antisense oligonucleotides, and small molecule inhibitors. Galunisertib (LY2157299 monohydrate is an oral small molecule inhibitor of the TGF-β receptor I kinase that specifically downregulates the phosphorylation of SMAD2, abrogating activation of the canonical pathway. Furthermore, galunisertib has antitumor activity in tumor-bearing animal models such as breast, colon, lung cancers, and hepatocellular carcinoma. Continuous long-term exposure to galunisertib caused cardiac toxicities in animals requiring adoption of a pharmacokinetic/pharmacodynamic-based dosing strategy to allow further development. The use of such a pharmacokinetic/pharmacodynamic model defined a therapeutic window with an appropriate safety profile that enabled the clinical investigation of galunisertib. These efforts resulted in an intermittent dosing regimen (14 days on/14 days off, on a 28-day cycle of galunisertib for all ongoing trials. Galunisertib is being investigated either as monotherapy or in combination with standard antitumor regimens (including nivolumab

  14. Different insulin concentrations in resuspended vs. unsuspended NPH insulin: Practical aspects of subcutaneous injection in patients with diabetes.

    Science.gov (United States)

    Lucidi, P; Porcellati, F; Marinelli Andreoli, A; Candeloro, P; Cioli, P; Bolli, G B; Fanelli, C G

    2017-06-06

    This study measured the insulin concentration (Ins [C] ) of NPH insulin in vials and cartridges from different companies after either resuspension (R+) or not (R-; in the clear/cloudy phases of unsuspended NPH). Measurements included Ins [C] in NPH(R+) and in the clear/cloudy phases of NPH(R-), and the time needed to resuspend NPH and time for NPH(R+) to separate again into clear/cloudy parts. In vials of NPH(R+) (assumed to be 100%), Ins [C] in the clear phase of NPH(R-) wasEli Lilly NPH, respectively. Likewise, in pen cartridges, Ins [C] in the clear phase of NPH(R-) wasLilly and Sanofi NPH. Time needed to resuspend NPH (spent in tipping) in vials was brief with both Novo (5±1s) and Lilly NPH (6±1s), but longer with all pen cartridges (50±8s, 40±6s and 30±4s from Novo, Lilly and Sanofi, respectively; P=0.022). Time required for 50% separation into cloudy and clear parts of NPH was longer with Novo (60±7min) vs. Lilly (18±3min) in vials (P=0.021), and affected by temperature, but not by the different diameter sizes of the vials. With pen cartridges, separation into clear and cloudy parts was significantly faster than in vials (P<0.01). Ins [C] in NPH preparations varies depending on their resuspension or not. Thus, subcutaneous injection of the same number of units of NPH in patients with diabetes may deliver different amounts of insulin depending on its prior NPH resuspension. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  15. Clinical outcomes with olanzapine long-acting injection: impact of the 3-hour observation period on patient satisfaction and well-being

    Directory of Open Access Journals (Sweden)

    Anand E

    2016-10-01

    Full Text Available Ernie Anand,1 Lovisa Berggren,2 John Landry,3 Ágoston Tóth,4 Holland C Detke5 1Neuroscience Medical Affairs, Eli Lilly & Company Ltd, Windlesham, UK; 2Global Statistical Sciences, Lilly Deutschland GmbH, Bad Homburg, Germany; 3Global Statistical Sciences, Eli Lilly Canada Inc., Toronto, ON, Canada; 4Neuroscience, Lilly Hungary, Budapest, Hungary; 5Psychiatry and Pain Disorders, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA Background: The objective of the present analysis is to determine the impact of the 3-hour observation period for olanzapine long-acting injection (LAI on patient satisfaction and well-being by comparing data collected before and after its implementation. Methods: This is a post hoc analysis of patients treated with olanzapine LAI in 1 a 6-month fixed-dose randomized controlled trial and/or 2 a 6-year open-label safety study. This analysis was limited to patients with schizophrenia who were treated with olanzapine LAI consistent with the approved indication and dosing recommendations of the European Union Summary of Product Characteristics (N=966. Of the 966 patients, the analysis further focused only on those patients who received both 1 at least one injection before the implementation of the 3-hour observation period and 2 at least one injection after implementation of the 3-hour observation period (N=487. Patient satisfaction was assessed with the three-item Patient Satisfaction with Medication Questionnaire-Modified. Responses were averaged across all postbaseline visits occurring before (ie, without the implementation of the 3-hour observation period and across all postbaseline visits occurring after (ie, with the implementation of the 3-hour observation period. In addition, the rate of postinjection delirium/sedation syndrome events was calculated. Results: There was no meaningful change after implementation of the 3-hour observation period in satisfaction (before: mean [SD] =4.0 [1.02] and

  16. Sleep disturbance in mental health problems and neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    Anderson KN

    2013-05-01

    Full Text Available Kirstie N Anderson1 Andrew J Bradley2,3 1Department of Neurology, Newcastle Upon Tyne Hospitals NHS Trust, Newcastle Upon Tyne, UK; 2Eli Lilly and Company Limited, Lilly House, Basingstoke, UK; 3Institute of Neuroscience, Newcastle University, Newcastle Upon Tyne, UK Abstract: Sleep has been described as being of the brain, by the brain, and for the brain. This fundamental neurobiological behavior is controlled by homeostatic and circadian (24-hour processes and is vital for normal brain function. This review will outline the normal sleep–wake cycle, the changes that occur during aging, and the specific patterns of sleep disturbance that occur in association with both mental health disorders and neurodegenerative disorders. The role of primary sleep disorders such as insomnia, obstructive sleep apnea, and REM sleep behavior disorder as potential causes or risk factors for particular mental health or neurodegenerative problems will also be discussed. Keywords: sleep, mental health, neurodegenerative disorders, cognition

  17. Commitment to leakless pumps

    International Nuclear Information System (INIS)

    Locheed, T.

    1993-01-01

    The landscape has changed radically in recent years. Not too long ago, Eli Lilly and Co.'s Clinton Laboratories plant in Clinton, IN, buried its solvent storage tanks because the company's insurer required the practice. At the time, tank burial was considered the safest way to handle the solvents. One of the materials stored in those tanks, methylene chloride (or dichloromethane, DCM), was considered a virtual godsend: it was clean, safe and inexpensive. More recently, DCM has acquired a tarnished reputation and a place on the EPA's most wanted list because of its extensive use in the United States (the EPA also regulates other solvents that Lilly uses, including acetone, toluene and methanol). As well as taking aim at fugitive emissions, more properly known as equipment leaks, the Clean Air Act Amendments specify that companies cannot store such chemicals underground in single-wall tanks any longer; secondary containment is the order of the day

  18. Developing an effective toxicology/quality assurance partnership. Improving quality, compliance, and cooperation.

    Science.gov (United States)

    Usher, R W

    1995-12-01

    Toxicology and Quality Assurance (QA) at Eli Lilly and Company are well integrated, yet still independent organizations that are aligned with the same overall business objective: to efficiently deliver a high-quality product to the customer. One of the keys to success has been the implementation of a monitoring/metric and trend analysis program of key work processes that are central to the delivery of final product. Our metrics program indicates that the multiple changes that we have made have resulted in a higher quality product. This paper will discuss the practical changes we have made as a part of our Total Quality journey. This article is based solely on the authors' experiences while at Eli Lilly and Company.

  19. Super Hydrides.

    Science.gov (United States)

    1988-03-01

    enantioselective synthesis Of the clinically important anti-depressants, (-)Tomoxetine, Fluoxetine (Prozac, Eli Lilly), and Nisoxetine (Scheme 1). Schem I a I...decade or so asymmetric synthesis has emerged from the cold to vie quite successfully with enzymes as a means of incorporating chirality in...with Chiral Alkoxyborohydrides. We have extended our synthesis of potassium dialkoxyborohydrides, K+IRB(OR’) 21- , conveniently prepared by the addition

  20. Résultats de recherche | Page 23 | CRDI - Centre de recherches ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Transition et amélioration des indices mondiaux de philanthropie. Cette subvention aide à transférer les activités d'élaboration des indices mondiaux de dons privés du Center for Global Prosperity de l'Hudson Institute à la Lilly Family School of Philanthropy de l'Université de l'Indiana. Projet ...

  1. Résultats de recherche | Page 10 | CRDI - Centre de recherches ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Cette subvention aide à transférer les activités d'élaboration des indices mondiaux de dons privés du Center for Global Prosperity de l'Hudson Institute à la Lilly Family School of Philanthropy de l'Université de l'Indiana. Projet. Réseau d'échanges et de recherche dans les deltas de l'océan Indien occidental. Le réseau ...

  2. Ensaios terapêuticos com penicilina: III - Bouba (Framboesia, pian, yaws: (continuação: penicilina de procedência americana, empregada em doses baixas também cura aparentemente esta enfermidade

    Directory of Open Access Journals (Sweden)

    A. M. da Cunha

    1944-10-01

    Full Text Available Five patients of yaws were treated with american Penicillin (Squibb, Winthrop and Lilly, in small dosis. The treatment has been performed, using 200 Oxford units each 4 hours. The total amount of units "per" subject, has varied from 24.000 to 54.000. A complete disappearence of the external lesions was obtained between the 12th and the 25th day of treatment.

  3. Toxic Hazards Research Unit Annual Technical Report: 1984

    Science.gov (United States)

    1984-09-01

    exposed to TOCP exhibited the classic lesions of delayed neuropathy (Smith and Lillie, 1931; Barnes and Denz, 1953; (avanagh, 1954; and Fenton , 1955...Safety of *.i Chemicals in Food, Drugs, and Cosmetics , The staff of the Divi- sion of Pharmacology of the Federal Food and Drug Administration, Austin...Annual Technical Report: 1967, AMRL-TR-67-137 (AD 834723), Aerospace Medical Research Laboratory, Wright-Patterson Air Force Base, Ohio. Fenton , J. C

  4. Context and Domain Knowledge Enhanced Entity Spotting in Informal Text

    Science.gov (United States)

    Gruhl, Daniel; Nagarajan, Meena; Pieper, Jan; Robson, Christine; Sheth, Amit

    This paper explores the application of restricted relationship graphs (RDF) and statistical NLP techniques to improve named entity annotation in challenging Informal English domains. We validate our approach using on-line forums discussing popular music. Named entity annotation is particularly difficult in this domain because it is characterized by a large number of ambiguous entities, such as the Madonna album "Music" or Lilly Allen's pop hit "Smile".

  5. The Ncar East in the 21st Century

    Directory of Open Access Journals (Sweden)

    Wigand Ritter

    2012-10-01

    Full Text Available Although an "avalanche of people" may be expected in thenear future lillie confidence seems to be justified with respect toa peaceful and prosperous development in the Near East. Politicalantagonism, often fuelled by religious intolerance threatei!Sor even pre1·ents the evaluation of promising opportunities atthis huge area between the Old World continents which couldotlwwise benefit so much from the by-passing great world trafficroutes.

  6. Résultats de recherche | Page 41 | CRDI - Centre de recherches ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Cette subvention aide à transférer les activités d'élaboration des indices mondiaux de dons privés du Center for Global Prosperity de l'Hudson Institute à la Lilly Family School of Philanthropy de l'Université de l'Indiana. Projet. Atténuer les risques de radicalisation violente chez les jeunes Maliens et Sénégalais. La région ...

  7. Molecular Mechanisms and Treatment Strategies for Obesity-Associated Coronary Artery Disease, an Imminent Military Epidemic

    Science.gov (United States)

    2007-12-01

    in response to another ‘hit.’ This two-hit model of UPR-induced apoptosis is critical to understanding how FC enrichment kills macrophages. In this...Schering- Plough Research Grant, 1989-1995, Responsible Investigator, $50,000 per annum Individual National Research Supplement Award for Postdoctoral...Association grant-in-aid study section (1994) Consultant for Merck, Schering- Plough , Warner-Lambert, Berlex, Eli Lilly, Pfizer, Talaria Biotech, ReddyUS

  8. Predictors of antipsychotic monotherapy with olanzapine during a 1-year naturalistic study of schizophrenia patients in Japan

    Directory of Open Access Journals (Sweden)

    Ye W

    2012-01-01

    Full Text Available Wenyu Ye1, Haya Ascher-Svanum2, Jennifer A Flynn3, Yuka Tanji3, Michihiro Takahashi3,41Lilly Suzhou Pharmaceutical Co, Shanghai, People's Republic of China; 2Eli Lilly and Company, Indianapolis, IN, USA; 3Lilly Research Laboratories Japan, Eli Lilly Japan K.K., Kobe, 4Terauchi-Takahashi Psychiatric Clinic, Ashiya, JapanPurpose: Although expert guidelines for the treatment of schizophrenia recommend antipsychotic monotherapy, the use of antipsychotic polypharmacy is common. This study identified characteristics that differentiate patients with schizophrenia who are treated with olanzapine monotherapy versus polypharmacy in usual care in Japan.Patients and methods: In a large (N = 1850 prospective, observational study, Japanese patients with schizophrenia who initiated treatment with olanzapine were followed for 1 year. Consistent with past research, antipsychotic polypharmacy was defined as the concurrent use of olanzapine and another antipsychotic for at least 60 days. Switching was defined as discontinuing a prior antipsychotic therapy rather than augmenting the medication regimen. Predictors of antipsychotic monotherapy were based on information available at the time of olanzapine initiation. Baseline characteristics were compared using t-tests and Χ2 tests. Stepwise logistic regression was used to identify independent predictors of monotherapy.Results: Patients treated with olanzapine monotherapy (43.2% differed from those treated with antipsychotic polypharmacy (56.8% on demographics, treatment history, baseline symptom levels, functional levels, and treatment-emergent adverse events. Stepwise logistic regression identified multiple variables that significantly predicted monotherapy: older age, shorter duration of schizophrenia, outpatient status, comorbid medical conditions, lower body mass index, no prior anticholinergic use, no prior mood stabilizer use, and switching from a previous antipsychotic (typical or atypical

  9. Inimeste teadlikkus arendab ravimiturgu / Rauno Pukonen ; ref. Enn Tosso

    Index Scriptorium Estoniae

    Pukonen, Rauno

    2003-01-01

    Ilmunud ka: Delovõje Vedomosti 15. okt. lk. 14. Eli Lilly juhatuse esimehe Rauno Pukoneni ettekandest Äripäeva konverentsil Äriplaan 2004. Ettekandja sõnul on Eesti ravimiturg ebaatraktiivne ja ettearvamatu, kompenseeritavate ravimite valik on kesine, Eesti tarbija jääb väga paljudest ravimitest ilma. Kommenteerib AS-i Magnum Medical juhatuse liige Tarmo Laanetu. Vt. samas: Ravimiturg riigi lõa otsas. Diagramm

  10. Morphological Characterization of the Frontal and Parietal Bones of the Human Skull

    Science.gov (United States)

    2017-03-01

    the image stack. Finally, the images were converted from gray scale to a binary format for the quantitative image analysis. An automated algorithm...validation with micro-CT. J of Anatomy . 2015;226(1):73–80. Lillie EM, Urban JE, Lynch SK, Weaver AA, Stitzel JD. Evaluation of skull cortical thickness... gray -level histograms. Automatica. 1975;11.285(296):23–27. Peterson J, Dechow PC. Material properties of the inner and outer cortical tables of the

  11. FLT-PET/CT as a Biomarker of Therapeutic Response in Pemetrexed Therapy for Non-Small Cell Lung Cancer

    Science.gov (United States)

    2016-12-01

    Teva Pharmaceuticals , Petach Tikva Israel) were provided freshly prepared as a 1mg/ml sterile saline solution by the Abramson Cancer Center...human and murine, pemetrexed (ALIMTA; Eli Lilly and Company, Indianapolis, IN) and cisplatin (Teva Pharmaceuticals , PetachTikva Israel) were provided...Griffiths JR, Doblas S, Sinkus R, Laverman P, Oyen WJ, Heerschap A, Boerman OC. Response Monitoring with [18F]FLT PET and Diffusion-Weighted MRI

  12. Associations between adherence and outcomes among older, type 2 diabetes patients: evidence from a Medicare Supplemental database

    Directory of Open Access Journals (Sweden)

    Boye KS

    2016-08-01

    Full Text Available Kristina Secnik Boye,1 Sarah E Curtis,1 Maureen J Lage,2 Luis-Emilio Garcia-Perez3 1Global Patient Outcomes and Real World Evidence, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 2HealthMetrics Outcomes Research, LLC, Bonita Springs, FL, 3Global Medical Affairs, Lilly Diabetes, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA Objective: To examine the association between adherence to glucose-lowering agents and patient outcomes, including costs, acute-care resource utilization, and complications, in an older, type 2 diabetic population.Data and methods: The study used Truven’s Medicare Supplemental database from July 1, 2009 to June 30, 2014. Patients aged 65 years or older were included if they had at least two type 2 diabetes diagnoses and received a glucose-lowering agent from July 1, 2010 through June 30, 2011. Multivariable analyses examined the relationships among 3-year patient outcomes and levels of adherence, proxied by the proportion of days covered. Outcomes included all-cause medical costs, diabetes-related medical costs, acute-care resource utilization, and acute complications.Results: In this study (N=123,235, higher adherence was linked to reduced costs and improved health outcomes. For example, comparing an individual with adherence of proportion of days covered <20% to one with proportion of days covered ≥80% illustrates an average saving of $28,824 in total 3-year costs. Furthermore, a 1% increase in adherence among 1,000 patients was associated with all-cause savings of $65,464 over 3 years. The probability of a hospitalization, an emergency room (ER visit, or an acute complication decreased monotonically as adherence levels got higher, as did the number of hospitalizations, ER visits, and days hospitalized (P<0.005.Conclusion: Higher adherence was associated with substantially less need for acute care, as indicated by a lowered probability of hospitalization or ER use, a reduced

  13. Does participation in a weight control program also improve clinical and functional outcomes for Chinese patients with schizophrenia treated with olanzapine?

    Directory of Open Access Journals (Sweden)

    Montgomery W

    2014-07-01

    Full Text Available William Montgomery,1 Tamas Treuer,2 Wenyu Ye,3 Hai Bo Xue,4 Sheng Hu Wu,4 Li Liu,4 Zbigniew Kadziola,5 Michael D Stensland,6 Haya Ascher-Svanum7 1Global Health Outcomes Eli Lilly Australia Pty Ltd, West Ryde, NSW, Australia; 2Neuroscience Research, Eli Lilly and Company, Budapest, Hungary; 3Global Statistical Sciences, Lilly Suzhou Pharmaceutical Company, Ltd, Shanghai, People's Republic of China; 4Medical Department, Lilly Suzhou Pharmaceutical Company, Ltd, Shanghai, People's Republic of China; 5Global Statistical Sciences, Eli Lilly GmbH, Vienna, Republic of Austria; 6Agile Outcomes Research, Inc., Rochester, MN, USA; 7Global Health Outcomes, Eli Lilly and Company, Indianapolis, IN, USA Objectives: This study examined whether participation in a weight control program (WCP by patients with schizophrenia treated with olanzapine was also associated with improvements in clinical and functional outcomes. Methods: A post-hoc analysis was conducted using data from the Chinese subgroup (n=330 of a multi-country, 6-month, prospective, observational study of outpatients with schizophrenia who initiated or switched to oral olanzapine. At study entry and monthly visits, participants were assessed with the Clinical Global Impression of Severity, and measures of patient insight, social activities, and work impairment. The primary comparison was between the 153 patients who participated in a WCP at study entry (n=93 or during the study (n=60 and the 177 patients who did not participate in a weight control program (non-WCP. Mixed Models for Repeated Measures with baseline covariates were used to compare outcomes over time. Kaplan–Meier survival analysis was used to assess time to response. Results: Participants had a mean age of 29.0 years and 29.3 years, and 51.0% and 57.6% were female for WCP and non-WCP groups, respectively. Average initiated daily dose for olanzapine was 9.5±5.4 mg. WCP participants gained less weight than non-participants (3.9 kg vs

  14. Dose study of the multikinase inhibitor, LY2457546, in patients with relapsed acute myeloid leukemia to assess safety, pharmacokinetics, and pharmacodynamics

    Directory of Open Access Journals (Sweden)

    Wacheck V

    2011-05-01

    Full Text Available Volker Wacheck1, Michael Lahn2, Gemma Dickinson3, Wolfgang Füreder4, Renata Meyer4, Susanne Herndlhofer4, Thorsten Füreder1, Georg Dorfner5, Sada Pillay2, Valérie André6, Timothy P Burkholder7, Jacqueline K Akunda8, Leann Flye-Blakemore9, Dirk Van Bockstaele9, Richard F Schlenk10, Wolfgang R Sperr4, Peter Valent4,111Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel, Vienna, Austria; 2Early Oncology Clinical Investigation, Eli Lilly and Company, Indianapolis, IN, USA; 3Department of Pharmacokinetics, Eli Lilly and Company, Erl Wood Research Centre, Windlesham, Surrey, UK; 4Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Währinger Gürtel, Vienna, Austria; 5Eli Lilly GesmbH, Medical Department, Vienna, Austria; 6Department of Statistics, Eli Lilly and Company, Erl Wood Research Centre, Surrey, UK; 7Discovery Chemistry Research and Technology, Eli Lilly and Company, Indianapolis, IN, USA; 8Nonclinical Toxicology, Eli Lilly and Company, Indianapolis, IN, USA; 9Flow Cytometry and Cell Analysis, Esoterix Clinical Trials Services, Mechelen, Belgium; 10Universitätsklinikum Ulm, Klinik für Innere Medizin III, Ulm, Germany; 11Ludwig Boltzmann Cluster Oncology, Vienna, AustriaBackground: Acute myeloid leukemia (AML is a life-threatening malignancy with limited treatment options in chemotherapy-refractory patients. A first-in-human dose study was designed to investigate a safe and biologically effective dose range for LY2457546, a novel multikinase inhibitor, in patients with relapsed AML.Methods: In this nonrandomized, open-label, dose escalation Phase I study, LY2457546 was administered orally once a day. Safety, pharmacokinetics, changes in phosphorylation of target kinases in AML blasts, and risk of drug–drug interactions (DDI were assessed.Results: Five patients were treated at the starting and predicted minimal biologically effective dose of 50 mg

  15. High heterogeneity and low reliability in the diagnosis of major depression will impair the development of new drugs.

    Science.gov (United States)

    Lieblich, Samuel M; Castle, David J; Pantelis, Christos; Hopwood, Malcolm; Young, Allan Hunter; Everall, Ian P

    2015-10-01

    Major depressive disorder is a common diagnosis associated with a high burden of disease that has proven to be highly heterogeneous and unreliable. Treatments currently available demonstrate limited efficacy and effectiveness. New drug development is urgently required but is likely to be hindered by diagnostic limitations. D.J.C. has received grants and personal fees from Eli Lilly, Janssen-Cilag, Roche, Allergen, Bristol-Myers Squibb, Pfizer, Lundbeck, AstraZeneca, Hospira, Organon, Sanofi-Aventis, and Wyeth during the writing of this review. C.P. has received grant support from Janssen-Cilag, Eli Lilly, Hospira (Mayne), AstraZeneca, and received honoraria for consultancy to Janssen-Cilag, Eli Lilly, Hospira (Mayne), AstraZeneca, Pfizer, Schering Plough, and Lundbeck. Over the past 2 years he has participated on advisory boards for Janssen-Cilag and Lundbeck, and received honoraria for talks presented at educational meetings organised by AstraZeneca, Janssen-Cilag and Lundbeck. M.H. has received personal fees or grants from Lundbeck, AstraZeneca and Servier during the writing of this review. A.H.Y. reports personal fees from Lundbeck, Sunovion, AstraZeneca and Janssen outside the submitted work. I.P.E. has received personal fees or grants from Lundbeck, AstraZeneca, and Abbvie during the writing of this review. © The Royal College of Psychiatrists 2015. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

  16. Recovery in patients with major depressive disorder (MDD: results of a 6-month, multinational, observational study

    Directory of Open Access Journals (Sweden)

    Novick D

    2017-10-01

    Full Text Available Diego Novick,1 William Montgomery,2 Ellen Vorstenbosch,3 Maria Victoria Moneta,3 Héctor Dueñas,4 Josep Maria Haro3 1Eli Lilly and Company, Windlesham, Surrey, UK; 2Eli Lilly Australia Pty Ltd, West Ryde, NSW, Australia; 3Parc Sanitari Sant Joan de Déu, Fundació Sant Joan de Déu, CIBERSAM, Universitat de Barcelona, Barcelona, Spain; 4Eli Lilly de Mexico, Mexico City, Mexico Abstract: Not all individuals treated for major depressive disorder (MDD achieve recovery. This observational study examined the recovery rates in MDD patients and the patient characteristics associated with achieving recovery in a naturalistic clinical setting. Recovery was defined as having both clinical and functional remission. Data for this post hoc analysis were taken from a 24-week prospective, observational study that involved 1,549 MDD patients. Clinical remission was assessed using the 16-item Quick Inventory of Depressive Symptomatology Self-Report and functional remission through the Sheehan Disability Scale and no days of reduced productivity in the previous week. Generalized estimating equation regression models were used to examine the baseline factors associated with recovery during follow-up. Clinical and functional remission was achieved in 70.6% and 56.1% of the MDD patients, respectively. MDD patients who achieved recovery (52.1% were significantly less likely to have impaired levels of functioning, concurrent medical or psychiatric conditions, low levels of education, or nonadherence to therapy at follow-up. The level of functioning during the index episode seems to be a better predictor of recovery than symptom severity. Therefore, the level of functioning should be considered while determining recovery from depression. Keywords: remission, functional impairment, clinical remission, course of illness, disability, predictors

  17. Comparison of patients undergoing switching versus augmentation of antipsychotic medications during treatment for schizophrenia

    Directory of Open Access Journals (Sweden)

    Ascher-Svanum H

    2012-03-01

    Full Text Available Haya Ascher-Svanum, Alan JM Brnabic, Anthony H Lawson, Bruce J Kinon, Virginia L Stauffer, Peter D Feldman, Katarina KelinLilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USAAbstract: It is often difficult to determine whether a patient may best benefit by augmenting their current medication or switching them to another. This post-hoc analysis compares patients’ clinical and functional profiles at the time their antipsychotic medications were either switched or augmented. Adult outpatients receiving oral antipsychotic treatment for schizophrenia were assessed during a 12-month international observational study. Clinical and functional measures were assessed at the time of first treatment switch/augmentation (0–14 days prior and compared between Switched and Augmented patient groups. Due to low numbers of patients providing such data, interpretations are based on effect sizes. Data at the time of change were available for 87 patients: 53 Switched and 34 Augmented. Inadequate response was the primary reason for treatment change in both groups, whereas lack of adherence was more prevalent in the Switched group (26.4% vs 8.8%. Changes in clinical severity from study initiation to medication change were similar, as indicated by Clinical Global Impressions–Severity scores. However, physical and mental component scores of the 12-item Short-Form Health Survey improved in the Augmented group, but worsened in the Switched group. These findings suggest that the patient’s worsening or lack of meaningful improvement prompts clinicians to switch antipsychotic medications, whereas when patients show some improvement, clinicians may be more likely to try bolstering the improvements through augmentation. Current findings are consistent with physicians’ stated reasons for switching versus augmenting antipsychotics in the treatment of schizophrenia. Confirmation of these findings requires further research

  18. A more rational approach to new-product development.

    Science.gov (United States)

    Bonabeau, Eric; Bodick, Neil; Armstrong, Robert W

    2008-03-01

    Companies often treat new-product development as a monolithic process, but it can be more rationally divided into two parts: an early stage that focuses on evaluating prospects and eliminating bad bets, and a late stage that maximizes the remaining candidates' market potential. Recognizing the value of this approach, Eli Lilly designed and piloted Chorus, an autonomous unit dedicated solely to the early stage. This article demonstrates how segmenting development in this way can speed it up and make it more cost-effective. Two classes of decision-making errors can impede NPD, the authors say. First, managers often ignore evidence challenging their assumptions that projects will succeed. As a result, many projects go forward despite multiple red flags; some even reach the market, only to fail dramatically after their introduction. Second, companies sometimes terminate projects prematurely because people fail to conduct the right experiments to reveal products' potential. Most companies promote both kinds of errors by focusing disproportionately on late-stage development; they lack the early, truth-seeking functions that would head such errors off. In segmented NPD, however, the early-stage organization maintains loyalty to the experiment rather than the product, whereas the late-stage organization pursues commercial success. Chorus has significantly improved NPD efficiency and productivity at Lilly. Although the unit absorbs just one-tenth of Lilly's investment in early-stage development, it delivers a substantially greater fraction of the molecules slated for late Phase II trials--at almost twice the speed and less than a third of the cost of the standard process, sometimes shaving as much as two years off the usual development time.

  19. Impact of anxiety symptoms on outcomes of depression: an observational study in Asian patients

    Directory of Open Access Journals (Sweden)

    Novick D

    2016-04-01

    Full Text Available Diego Novick,1 William Montgomery,2 Jaume Aguado,3 Xiaomei Peng,4 Josep Maria Haro3 1Eli Lilly and Company, Windlesham, Surrey, UK; 2Eli Lilly Australia Pty Ltd, West Ryde, NSW, Australia; 3Parc Sanitari Sant Joan de Déu, CIBERSAM, Universitat de Barcelona, Barcelona, Spain; 4Eli Lilly and Company, Indianapolis, IN, USA Objective: To investigate the impact of anxiety symptoms on depression outcomes in Asian patients with major depressive disorder (MDD (n=714. Methods: The 17-item Hamilton Depression Scale (HAMD-17, overall severity, somatic symptoms, and quality of life (QOL (EuroQOL Questionnaire-5 Dimensions [EQ-5D] were assessed at baseline and 3 months. Anxiety was measured using items 10 and 11 from the HAMD-17. Linear, tobit, and logistic multiple regression models analyzed the impact of anxiety symptoms on outcomes. Baseline anxiety was related to age and the presence of pain symptoms at baseline. Results: Regression models showed that a higher level of anxiety was associated with a lower frequency of remission and lower QOL at 3 months. Patients with lower baseline anxiety symptoms had higher remission rates (odds ratio for each point of anxiety symptoms, 0.829 [95% confidence interval [CI]: 0.723–0.951]. Patients with higher levels of baseline anxiety had a lower QOL at 3 months (a decrease in EQ-5D tariff score for each point of anxiety symptoms, 0.023 [95% CI: 0.045–0.001]. Conclusion: In conclusion, the presence of anxiety symptoms negatively impacts the outcomes of depression. Keywords: depression, anxiety, Asia, observational, outcomes

  20. Experimental validation of large-eddy simulation for swirling methane-air non-premixed combustion

    Energy Technology Data Exchange (ETDEWEB)

    Hu, L.Y.; Luo, Y.H.; Xu, C.S. [Shanghai Jiaotong Univ. (China). School of Mechanical Engineering; Zhou, L.X. [Tsinghua Univ., Beijing (China). Dept. of Engineering Mechanics

    2013-07-01

    Large-eddy simulation of swirling methane-air non-premixed combustion was carried out using a Smagorinsky-Lilly subgrid scale stress model and a presumed-PDF fast-chemistry combustion model. The LES statistical results are validated by PIV, temperature and species concentration measurements made by the present authors. The results indicate that in the present case the presumed-PDF fast-chemistry combustion model is a fairish one. The instantaneous vorticity and temperature maps show clearly the development and the interaction between coherent structures and combustion.

  1. Large-eddy simulation of swirling pulverized-coal combustion

    Energy Technology Data Exchange (ETDEWEB)

    Hu, L.Y.; Luo, Y.H. [Shanghai Jiaotong Univ. (China). School of Mechanical Engineering; Zhou, L.X.; Xu, C.S. [Tsinghua Univ., Beijing (China). Dept. of Engineering Mechanics

    2013-07-01

    A Eulerian-Lagrangian large-eddy simulation (LES) with a Smagorinsky-Lilly sub-grid scale stress model, presumed-PDF fast chemistry and EBU gas combustion models, particle devolatilization and particle combustion models are used to study the turbulence and flame structures of swirling pulverized-coal combustion. The LES statistical results are validated by the measurement results. The instantaneous LES results show that the coherent structures for pulverized coal combustion is stronger than that for swirling gas combustion. The particles are concentrated in the periphery of the coherent structures. The flame is located at the high vorticity and high particle concentration zone.

  2. Systematic review of raloxifene in postmenopausal Japanese women with osteoporosis or low bone mass (osteopenia

    Directory of Open Access Journals (Sweden)

    Fujiwara S

    2014-11-01

    Full Text Available Saeko Fujiwara,1 Etsuro Hamaya,2 Masayo Sato,2 Peita Graham-Clarke,3 Jennifer A Flynn,2 Russel Burge41Hiroshima Atomic Bomb Casualty Council, Hiroshima, Japan; 2Lilly Research Laboratories Japan, Eli Lilly Japan K.K., Kobe, Japan; 3Global Health Outcomes, Eli Lilly Australia, Sydney, NSW, Australia; 4Global Health Outcomes, Eli Lilly and Company, Indianapolis, IN, USAPurpose: To systematically review the literature describing the efficacy, effectiveness, and safety of raloxifene for postmenopausal Japanese women with osteoporosis or low bone mass (osteopenia.Materials and methods: Medline via PubMed and Embase was systematically searched using prespecified terms. Retrieved publications were screened and included if they described randomized controlled trials or observational studies of postmenopausal Japanese women with osteoporosis or osteopenia treated with raloxifene and reported one or more outcome measures (change in bone mineral density [BMD]; fracture incidence; change in bone-turnover markers, hip structural geometry, or blood–lipid profile; occurrence of adverse events; and change in quality of life or pain. Excluded publications were case studies, editorials, letters to the editor, narrative reviews, or publications from non-peer-reviewed journals; multidrug, multicountry, or multidisease studies with no drug-, country-, or disease-level analysis; or studies of participants on dialysis.Results: Of the 292 publications retrieved, 15 publications (seven randomized controlled trials, eight observational studies were included for review. Overall findings were statistically significant increases in BMD of the lumbar spine (nine publications, but not the hip region (eight publications, a low incidence of vertebral fracture (three publications, decreases in markers of bone turnover (eleven publications, improved hip structural geometry (two publications, improved blood–lipid profiles (five publications, a low incidence of hot flushes

  3. Strategic Performance Measurement of Research and Development

    DEFF Research Database (Denmark)

    Parisi, Cristiana; Rossi, Paola

    2015-01-01

    The paper used an in depth case study to investigate how firms can integrate the strategic performance measurement of R&D with the Balanced Scorecard. Moreover, the paper investigated the crucial role of controller in the decision making process of this integration.The literature review of R......-financial ratio as the R&D measures to introduce in the Balanced Scorecard.In choosing our case study, we have selected the pharmaceutical industry because of its relevant R&D investment. Within the sector we chose the Italian affiliate of a traditional industry leader, Eli Lilly Italia,that was characterized...

  4. Jutuvõistluse "Musta mantliga mees" võitis Katrin Johanson

    Index Scriptorium Estoniae

    2007-01-01

    Eduard Vilde muuseumi poolt läbi viidud krimi- ja põnevusjuttude võistlusest "Musta mantliga mees". Žürii: Karl Martin Sinijärv, Juhan Habicht, Paul Pajos, Rebekka Lotman, Kristin Rammus, Piret Meos.Võitja: Katrin Johanson, teine koht: Taavet Kase, kolmas koht: Imre Kõuts. Ajalehe "Postimees" eriauhinnad said: Juhan Voolaid, Hella Riisalu, Stina Maria Vilt, Sirle Poikkanen, Märt Kivimäe. Tallinna noorte infokeskuse auhinnad: Juhan Voolaid, Sirle Poikkalainen, Lilli Anderson, Aino Rätsep. Eduard Vilde muuseumi eriauhinnad: Merilin Jürjo, Laura Pirso

  5. Do concomitant pain symptoms in patients with major depression affect quality of life even when taking into account baseline depression severity?

    Directory of Open Access Journals (Sweden)

    Novick D

    2013-05-01

    Full Text Available Diego Novick,1 William Montgomery,2 Zbigniew Kadziola,3 Victoria Moneta,4 Xiaomei Peng,5 Roberto Brugnoli,6 Josep Maria Haro41Eli Lilly and Company, Windlesham, Surrey, UK; 2Eli Lilly Australia Pty Ltd, West Ryde, NSW, Australia; 3Eli Lilly Austria GmbH, Vienna, Austria; 4Parc Sanitari Sant Joan de Déu, Fundació Sant Joan de Déu, CIBERSAM, Universitat de Barcelona, Barcelona, Spain; 5Eli Lilly and Company, Indianapolis, IN, USA; 6Università di Roma, “Sapienza,” Rome, ItalyBackground: Patients with major depressive disorder (MDD may suffer from concomitant pain symptoms. The aim of this study is to determine whether the presence of painful physical symptoms (PPS influences quality of life when taking into account baseline depression severity.Methods: Patients with a new or first episode of MDD (n = 909 were enrolled in a 3-month prospective observational study in East Asia. The Hamilton Depression Rating Scale, Clinical Global Impression-Severity score, Somatic Symptom Inventory, and EuroQoL questionnaire-5 Dimensions (EQ-5D and EQ-Visual Analogue Scale (EQ-VAS were assessed at baseline and 3 months’ follow-up. The presence of PPS was defined as a mean score of ≥2 on the Somatic Symptom Inventory pain-related items. Regression analyses determined predictors of quality of life at 3 months, adjusting for age, sex, depressive symptoms, overall severity, and quality of life at baseline.Results: PPS were present (PPS+ at baseline in 52% of patients. During the 3-month follow-up, EQ-VAS scores improved from 47.7 (standard deviation [SD] 20.6 to 72.5 (SD 20.4, and EQ-5D improved from 0.48 (SD 0.34 to 0.80 (SD 0.26. At 3 months, mean EQ-VAS was 66.4 (SD 21.2 for baseline PPS+ patients versus 78.5 (SD 17.6 for baseline PPS- patients, and mean EQ-5D was 0.71 (SD 0.29 versus 0.89 (SD 0.18. PPS+ at baseline was a significant predictor of quality of life at 3 months after adjusting for sociodemographic and baseline clinical variables

  6. The current status of immunotoxins: an overview of experimental and clinical studies as presented at the Third International Symposium on Immunotoxins.

    Science.gov (United States)

    Uckun, F M; Frankel, A

    1993-02-01

    The Third International Symposium on Immunotoxins was held on June 19-21, 1992 in Orlando, Florida. This symposium was sponsored by NATO, NIH, Pierce Chemical Company, Walt Disney Cancer Institute at Florida Hospital, Duke Comprehensive Cancer Center, Xoma, Immunogen, Seragen, Bristol-Myers Squibb, Chiron, Ortho Biotech, Upjohn, Merck Sharp & Dohme Research Laboratories, Abbot Laboratories, Lilly Research Laboratories, and Evans & Sutherland. The Pierce Immunotoxin Award which recognizes outstanding contributions to immunotoxin research and development, was presented to Drs David FitzGerald, Fatih Uckun, David Eisenberg, and Ira Wool, for their contributions to the immunotoxin field.

  7. Nava tiigi ääres seiklevad Hunt ja Rebane / Liisi Seil ; kommenteerinud Pille Põllumäe

    Index Scriptorium Estoniae

    Seil, Liisi, 1971-

    2009-01-01

    17.-19. juulini Lilli külas Nava talus toimuvast 4. Nava lava festivalist. 19. 07 mängib Karksi valla kultuurikeskuse noorteteater "O" lasteetendust "Hundi ja Rebase lend lõunanabale", mille on Nava talu peremehe Jaak Kõdari raamatu "Kriimureinulised lood. 3, Argonaudid" põhjal kirjutanud ja lavastanud Silvia Soro. Kostüümid tegi Thea Ilusmets. 17., 18. ja 19. 07 mängitakse Jaak Kõdari mulgikeelset külanäitemängu "Kõik läheb mööda, kõik tuleb jälle. 1912-1918", lavastaja Silvia Soro

  8. Transition probabilities and radiative decay constants of the excited levels of Ne

    International Nuclear Information System (INIS)

    Wosinski, L.

    1981-01-01

    Transition probabilities for eight optical transitions between the 3p and 3d neon levels have been measured by the ''plasma transparency method''. The transitions probabilities are placed on an absolute scale by use of the recently reported values for the 4p→3s transitions. The measurements of induced changes in populations allowed the determination of the ratios of the radiative decay constants for the 4p and 3d levels. The experimental results are compared with the theoretically calculated transitions probabilities of Murphy and Lilly. (author)

  9. Examining the Effect of Medication Adherence on Risk of Subsequent Fracture Among Women with a Fragility Fracture in the U.S. Medicare Population.

    Science.gov (United States)

    Keshishian, Allison; Boytsov, Natalie; Burge, Russel; Krohn, Kelly; Lombard, Louise; Zhang, Xiang; Xie, Lin; Baser, Onur

    2017-11-01

    In the United States, osteoporosis affects approximately 10 million people, of whom 80% are women, and it contributes a significant clinical burden to the community. Poor adherence to osteoporosis medications adds to the overall burden of illness. To examine the association of osteoporosis medication adherence and the risk of a subsequent fracture among Medicare-enrolled women with a previous fragility fracture. This study was a retrospective observational analysis of U.S. administrative claims data among female Medicare beneficiaries who had a nontrauma closed fragility fracture between January 1, 2011, and December 31, 2011. Patients were required to have continuous medical and pharmacy enrollment 12 months pre- and postfracture date. In addition, patients were required to have an osteoporosis medication prescription for a bisphosphonate (alendronate, risedronate, pamidronate, etidronate, zoledronate, and tiludronate), calcitonin, denosumab, raloxifene, or teriparatide during the follow-up period. Adherence was calculated using cumulative medication possession ratio (MPR) from the treatment initiation date in 30-day increments. MPR was stratified into high adherence (MPR ≥ 80%), moderate adherence (50% ≤ MPR > 80%), and low adherence (MPR 80%; n = 4,602, 16.6%). After adjusting for demographics and clinical characteristics, patients with low and moderate adherence to osteoporosis medications were 33% (hazard ratio [HR] = 1.33; 95% CI = 1.17-1.50, P Eli Lilly. Xie, Keshishian, and Baser are employees of STATinMED Research, a paid consultant to Eli Lilly in connection with the study design, data analysis, and development of the manuscript for this study. Boytsov, Burge, Lombard, and Zhang are employees and stock owners of Eli Lilly. At the time of research, Krohn was an employee of Eli Lilly. Study concept and design were contributed by Burge and Lombard, along with the other authors. Xie, Baser, and Keshishian took the lead in data collection, assisted by the

  10. Dosing of U-100 insulin and associated outcomes among Medicare enrollees with type 1 or type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Eby EL

    2015-06-01

    Full Text Available Elizabeth L Eby,1 Kate Van Brunt,2 Cynthia Brusko,3 Bradley Curtis,4 Maureen J Lage5 1Global Patient Outcomes and Real World Evidence, Eli Lilly and Co., Indianapolis IN USA; 2Eli Lilly and Co., Windlesham, UK; 3Lilly USA, LLC, Indianapolis, IN, USA; 4Eli Lilly and Co., Indianapolis, IN, USA; 5HealthMetrics Outcomes Research, LLC, Bonita Springs, FL, USA Objective: To examine costs, resource utilization, adherence, and hypoglycemic events among various doses of U-100 insulin regimens among elderly patients (age ≥65 years diagnosed with diabetes.Methods: Truven Health Analytics Medicare databases from January 1, 2008 through December 31, 2011 were utilized. General linear models with a gamma distribution and log link were used to examine costs, while logistic and negative binomial regressions were used to examine resource utilization and hypoglycemic events. Analyses controlled for patient characteristics, pre-period comorbidities, general health, and use of antidiabetic medications as well as index dose of insulin.Results: All-cause inpatient, emergency room, and outpatients costs, as well as diabetes-related inpatient costs, were highest among individuals who were treated with an index dose of 10–100 units/day followed by >300 units/day, while drug costs and total costs generally increased as index dosage increased. Resource utilization generally followed the same pattern as costs, with number of office visits increasing as the dose increased and the highest hospital length of stay, number of hospitalizations, number of emergency room visits, and number of diabetes-related hospitalizations were generally highest among those in the lowest and highest index dose cohorts. Compared to patients who initiated with an index dose of 10–100 units/day, all other patients were significantly less likely to achieve an adherence threshold of 80% based upon index dose range, and while those with an index dose of >100–150 units/day were

  11. Predictors of continuation with olanzapine during the 1-year naturalistic treatment of patients with schizophrenia in Japan

    Directory of Open Access Journals (Sweden)

    Ye W

    2011-12-01

    Full Text Available Wenyu Ye1, Haya Ascher-Svanum2, Yuka Tanji3, Jennifer A Flynn3, Michihiro Takahashi3,41Lilly Suzhou Pharmaceutical Co, Shanghai, People’s Republic of China; 2Eli Lilly and Company, Indianapolis, IN, USA; 3Lilly Research Laboratories Japan, Eli Lilly Japan KK, Kobe, 4Terauchi-Takahashi Psychiatric Clinic, Ashiya, JapanPurpose: Treatment continuation is considered an important measure of antipsychotic effectiveness in schizophrenia, reflecting the medication’s efficacy, safety, and tolerability from both patients’ and clinicians’ perspectives. This study identified characteristics of patients with schizophrenia who continue olanzapine therapy for a 1-year period in Japan.Methods: In a large (N = 1850, prospective, observational study, Japanese patients with schizophrenia who initiated treatment with olanzapine were followed for 1 year. Baseline characteristics were compared using t-tests and chi-square tests. Stepwise logistic regression was used to identify independent baseline predictors of treatment continuation.Results: Most patients (68.2% continued with olanzapine therapy for the full 1-year study period, with an average duration of 265.5 ± 119.4 days. At baseline, patients who continued were significantly more likely to be male, older, and inpatients; have longer illness duration, higher negative and cognitive symptoms, better health-related quality of life, and prior anticholinergic use. Continuers were significantly less likely to engage in social activities, live independently, work for pay, or have prior antidepressant use. Continuers showed significantly greater early (3-month improvement in global symptom severity. Logistic regression found that continuation was significantly predicted by longer illness duration, lower positive symptoms, higher negative symptoms, and better health-related quality of life.Conclusions: In this large naturalistic study in Japan, most patients with schizophrenia stayed on olanzapine therapy for

  12. 2008. aasta tõlkeilukirjandus / Kätlin Kaldmaa

    Index Scriptorium Estoniae

    Kaldmaa, Kätlin, 1970-

    2009-01-01

    Ülevaade 2008. aastal Eestis ilmunud tõlkeilukirjandusest. Pikemalt käsitletakse järgmisi autoreid ja nende teoseid: Margaret Atwood "Ebakõlad", William Faulkner "Absalom! Absalom!", Cormac McCarthy "Tee", Halldór Laxness "Islandi kell", T. H. White "Kunagine ja tulevane kuningas", Guillermo Martínez "Märkamatud mõrvad", Charlotte Weitze "Pimeduse pärusmaa", Daniel Kehlmann "Maailma mõõtmine", Milorad Pavić "Tuule sisemine pool, ehk, Romaan Herost ja Leandrosest", Michel Houellebecq "Elementaarosakesed", Marguerite Duras "Põhja-Hiina armuke", Haruki Murakami "Kafka mererannas", Anne Birkefeldt Radge "Berliini paplid", "Erakvähid" ja "Rohelised aasad", Linn Ullmann "Õnnistatud laps", Lars Saabye Christensen "Modell", Jon Fosse "See on Ales", Peter Høeg "Vaikne tüdruk", Leena Krohn "Matemaatilised olendid", Käbi Laretei "Kuhu kadus kõik see armastus?", E. M. Forster "Teekond Indiasse", Rudyard Kipling "Lispeth", Asha Miró ja Anna Soler-Pont "Sandlipuu jäljed", Khaled Hosseini "Lohejooksja", Billy Collins "Allegooria surm", Wisława Szymborska "Oma aja lapsed", Zbigniew Herbert "Valitud luuletused", Carlos Vitale "Kohaühtsus", Jüri Talvet (koostaja) "Ameerika luule antoloogia", Marjane Satrapi "Persepolis", Hergé "Sinine lootos" ja "Vaarao sigar", Sinikka Nopola "Risto Räppar ja kohutav vorst" ja "Risto Räppar ja viimane hoiatus", Espen Fyksen ja Øyvind Rune Stålen "Elias, väike päästekaater", Hannu Mäkelä "Miisa uus pere", Timo Parvela "Kiigelaud", Nick Hornby "Maoli", Pierre Bayard "Kuidas rääkida raamatutest, mida me pole lugenud", Milan Kundera "Eesriie", Georges Perec "Mõelda/liigitada ja teisi tekste"

  13. Open innovation for phenotypic drug discovery: The PD2 assay panel.

    Science.gov (United States)

    Lee, Jonathan A; Chu, Shaoyou; Willard, Francis S; Cox, Karen L; Sells Galvin, Rachelle J; Peery, Robert B; Oliver, Sarah E; Oler, Jennifer; Meredith, Tamika D; Heidler, Steven A; Gough, Wendy H; Husain, Saba; Palkowitz, Alan D; Moxham, Christopher M

    2011-07-01

    Phenotypic lead generation strategies seek to identify compounds that modulate complex, physiologically relevant systems, an approach that is complementary to traditional, target-directed strategies. Unlike gene-specific assays, phenotypic assays interrogate multiple molecular targets and signaling pathways in a target "agnostic" fashion, which may reveal novel functions for well-studied proteins and discover new pathways of therapeutic value. Significantly, existing compound libraries may not have sufficient chemical diversity to fully leverage a phenotypic strategy. To address this issue, Eli Lilly and Company launched the Phenotypic Drug Discovery Initiative (PD(2)), a model of open innovation whereby external research groups can submit compounds for testing in a panel of Lilly phenotypic assays. This communication describes the statistical validation, operations, and initial screening results from the first PD(2) assay panel. Analysis of PD(2) submissions indicates that chemical diversity from open source collaborations complements internal sources. Screening results for the first 4691 compounds submitted to PD(2) have confirmed hit rates from 1.6% to 10%, with the majority of active compounds exhibiting acceptable potency and selectivity. Phenotypic lead generation strategies, in conjunction with novel chemical diversity obtained via open-source initiatives such as PD(2), may provide a means to identify compounds that modulate biology by novel mechanisms and expand the innovation potential of drug discovery.

  14. Root cause investigation of a viral contamination incident occurred during master cell bank (MCB) testing and characterization--a case study.

    Science.gov (United States)

    Chen, Dayue; Nims, Raymond; Dusing, Sandra; Miller, Pamela; Luo, Wen; Quertinmont, Michelle; Parekh, Bhavin; Poorbaugh, Josh; Boose, Jeri Ann; Atkinson, E Morrey

    2008-11-01

    An adventitious agent contamination occurred during a routine 9 CFR bovine viral screening test at BioReliance for an Eli Lilly Chinese Hamster Ovary (CHO) cell-derived Master Cell Bank (MCB) intended for biological production. Scientists from the sponsor (Eli Lilly and Company) and the testing service company (BioReliance) jointly conducted a systematic investigation in an attempt to determine the root cause of the contamination. Our investigation resulted in the identification of the viral nature of the contaminant. Subsequent experiments indicated that the viral contaminant was a non-enveloped and non-hemadsorbing virus. Transmission electron microscopy (TEM) revealed that the viral contaminant was 25-30 nm in size and morphologically resembled viruses of the family Picornaviridae. The contaminant virus was readily inactivated when exposed to acidic pH, suggesting that the viral contaminant was a member of rhinoviruses. Although incapable of infecting CHO cells, the viral contaminant replicated efficiently in Vero cell with a life cycle of approximately 16 h. Our investigation provided compelling data demonstrating that the viral contaminant did not originate from the MCB. Instead, it was introduced into the process during cell passaging and a possible entry point was proposed. We identified the viral contaminant as an equine rhinitis A virus using molecular cloning and DNA sequencing. Finally, our investigation led us to conclude that the source of the viral contaminant was the equine serum added to the cell growth medium in the 9 CFR bovine virus test.

  15. Continuous flow technology vs. the batch-by-batch approach to produce pharmaceutical compounds.

    Science.gov (United States)

    Cole, Kevin P; Johnson, Martin D

    2018-01-01

    For the manufacture of small molecule drugs, many pharmaceutical innovator companies have recently invested in continuous processing, which can offer significant technical and economic advantages over traditional batch methodology. This Expert Review will describe the reasons for this interest as well as many considerations and challenges that exist today concerning continuous manufacturing. Areas covered: Continuous processing is defined and many reasons for its adoption are described. The current state of continuous drug substance manufacturing within the pharmaceutical industry is summarized. Current key challenges to implementation of continuous manufacturing are highlighted, and an outlook provided regarding the prospects for continuous within the industry. Expert commentary: Continuous processing at Lilly has been a journey that started with the need for increased safety and capability. Over twelve years the original small, dedicated group has grown to more than 100 Lilly employees in discovery, development, quality, manufacturing, and regulatory designing in continuous drug substance processing. Recently we have focused on linked continuous unit operations for the purpose of all-at-once pharmaceutical manufacturing, but the technical and business drivers that existed in the very beginning for stand-alone continuous unit operations in hybrid processes have persisted, which merits investment in both approaches.

  16. The riddle of sex: biological theories of sexual difference in the early twentieth-century.

    Science.gov (United States)

    Ha, Nathan Q

    2011-01-01

    At the turn of the twentieth century, biologists such as Oscar Riddle, Thomas Hunt Morgan, Frank Lillie, and Richard Goldschmidt all puzzled over the question of sexual difference, the distinction between male and female. They all offered competing explanations for the biological cause of this difference, and engaged in a fierce debate over the primacy of their respective theories. Riddle propounded a metabolic theory of sex dating from the late-nineteenth century suggesting that metabolism lay at the heart of sexual difference. Thomas Hunt Morgan insisted on the priority of chromosomes, Frank Lillie emphasized the importance of hormones, while Richard Goldschmidt supported a mixed model involving both chromosomes and hormones. In this paper, I will illustrate how the older metabolic theory of sex was displaced when those who argued for the relatively newer theories of chromosomes and hormones gradually formed an alliance that accommodated each other and excluded the metabolic theory of sex. By doing so, proponents of chromosomes and hormones established their authority over the question of sexual difference as they laid the foundations for the new disciplines of genetics and endocrinology. Their debate raised urgent questions about what constituted sexual difference, and how scientists envisioned the plasticity and controllability of this difference. These theories also had immediate political and cultural consequences at the turn of the twentieth century, especially for the eugenic and feminist movements, both of which were heavily invested in knowledge of sex and its determination, ascertainment, and command.

  17. JAK1/2 inhibition with baricitinib in the treatment of autoinflammatory interferonopathies.

    Science.gov (United States)

    Sanchez, Gina A Montealegre; Reinhardt, Adam; Ramsey, Suzanne; Wittkowski, Helmut; Hashkes, Philip J; Berkun, Yackov; Schalm, Susanne; Murias, Sara; Dare, Jason A; Brown, Diane; Stone, Deborah L; Gao, Ling; Klausmeier, Thomas; Foell, Dirk; Jesus, Adriana A de; Chapelle, Dawn C; Kim, Hanna; Dill, Samantha; Colbert, Robert; Failla, Laura; Kost, Bahar; O'Brien, Michelle; Reynolds, James C; Folio, Les R; Calvo, Katherine R; Paul, Scott M; Weir, Nargues; Brofferio, Alessandra; Soldatos, Ariane; Biancotto, Angélique; Cowen, Edward W; Digiovanna, John G; Gadina, Massimo; Lipton, Andrew J; Hadigan, Colleen; Holland, Steven M; Fontana, Joseph; Alawad, Ahmad S; Brown, Rebecca J; Rother, Kristina I; Heller, Theo; Brooks, Kristina M; Kumar, Parag; Brooks, Stephen R; Waldman, Meryl; Singh, Harsharan K; Nickeleit, Volker; Silk, Maria; Prakash, Apurva; Janes, Jonathan M; Ozen, Seza; Wakim, Paul G; Brogan, Paul A; Macias, William L; Goldbach-Mansky, Raphaela

    2018-04-12

    Monogenic Interferon (IFN)-mediated autoinflammatory diseases present in infancy with systemic inflammation, an IFN-response-gene-signature (IRS), inflammatory organ damage and high mortality. We used the janus kinase (JAK) inhibitor baricitinib with IFN-blocking activity in vitro, to ameliorate disease. Between October 2011 and February 2017, 10 patients with CANDLE (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures), 4 with SAVI (Stimulator of IFN genes (STING)-associated vasculopathy with onset in infancy), and 4 patients with other interferonopathies were enrolled in an Expanded Access Program. Patients underwent dose-escalation, benefit was assessed by reductions in daily disease symptoms and corticosteroid requirement. Quality-of-life, organ inflammation, changes in IFN-induced biomarkers, and safety were longitudinally assessed. 18 patients were treated for a mean duration of 3.0 years (1.5-4.9 years). The median daily symptom score decreased from 1.3 (IQR 0.93-1.78) to 0.25 (IQR 0.1-0.63) (P Eli Lilly. Eli Lilly is the sponsor of the compassionate use program.

  18. The promotion of olanzapine in primary care: an examination of internal industry documents.

    Science.gov (United States)

    Spielmans, Glen I

    2009-07-01

    Media reports have discussed how olanzapine was marketed off-label for dementia and subsyndromal bipolar disorder. Much of this marketing occurred in primary care settings. However, these reports have provided few details. In legal proceedings, Lilly disclosed internal documents that detail the strategies utilized to market olanzapine. The current paper addresses the marketing of olanzapine in detail based upon a review of these documents. All 358 documents released by Lilly are publicly available online. Documents were utilized for this review if they were relevant to the marketing of olanzapine in primary care settings in the United States. It was found that olanzapine was marketed off-label in primary care settings for relatively mild symptoms that were framed as bipolar disorder and schizophrenia. A key strategy in this campaign was the use of hypothetical patient profiles in detailing visits, most of which clearly failed to meet diagnostic criteria for any recognized mental disorder. Evidence emerged that olanzapine was also marketed off-label as a treatment for dementia.

  19. Patient Characteristics, Health Care Resource Utilization, and Costs Associated with Treatment-Regimen Failure with Biologics in the Treatment of Psoriasis.

    Science.gov (United States)

    Foster, Shonda A; Zhu, Baojin; Guo, Jiaying; Nikai, Enkeleida; Ojeh, Clement; Malatestinic, William; Goldblum, Orin; Kornberg, Lori J; Wu, Jashin J

    2016-04-01

    variance for continuous variables and chi-square tests for categorical variables without adjustment. Cost differences were compared using the propensity score-adjusted bin bootstrapping method. Overall, 2,146 patients met the enrollment criteria. The mean age was 45.1 years. Of these patients, 41.5% were considered treatment-regimen failures. Among treatment-regimen failures, 53% were females, and among non-treatment-regimen failures, 61% were male. Patients who experienced treatment-regimen failure had higher incidences of comorbid cerebrovascular disease, hypertension, chronic pulmonary disease, depression, and anxiety in the pre-index period and were more likely to use concomitant topicals (67.0% vs. 58.4%; P different characteristics and incurred higher all-cause health care costs than did patients without treatment-regimen failure during the pre-index period. This study was supported by Eli Lilly and Company. Foster, Zhu, Guo, Nikai, Malatestinic, Ojeh, and Goldblum are full-time employees and stockholders of Eli Lilly and Company. Kornberg is a full-time employee of INC Research, which was contracted by Eli Lilly to assist with medical writing. Wu has received research funding from AbbVie, Amgen, Coherus Biosciences, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Regeneron, and Sandoz; he is a consultant for AbbVie, Amgen, Celgene, Dermira, DUSA Pharmaceuticals, Eli Lilly, and Pfizer. Study concept was developed by Foster, Ojeh, Malatestinic, and Goldblum. Zhu and Guo, along with Foster, took the lead in data collection, and data interpretation was performed by Nikai, Wu, and Foster, with assistance from the other authors. The manuscript was primarily written by Kornberg, along with Foster, with assistance from the other authors. All of the authors were involved with manuscript revision.

  20. Effectiveness and safety of oral olanzapine treatment transitioned from rapid-acting intramuscular olanzapine for agitation associated with schizophrenia

    Directory of Open Access Journals (Sweden)

    Katagiri H

    2018-04-01

    Full Text Available Hideaki Katagiri,1 Masanori Taketsuna,2 Shinpei Kondo,3 Kenta Kajimoto,4 Etsuko Aoi,5 Yuka Tanji1 1Bio-Medicines, Medicines Development Unit Japan, Eli Lilly Japan K.K., Kobe, Japan; 2Statistical Sciences, Medicines Development Unit Japan, Eli Lilly Japan K.K., Kobe, Japan; 3Post Marketing Study Management, Medicines Development Unit Japan, Eli Lilly Japan K.K., Kobe, Japan; 4Scientific Communications, Medicines Development Unit Japan, Eli Lilly Japan K.K., Kobe, Japan; 5Global Patient Safety Japan, Quality and Patient Safety, Eli Lilly Japan K.K., Kobe, Japan Objective: To assess the effectiveness and safety of oral olanzapine treatment transitioned from rapid-acting intramuscular olanzapine (RAIM in patients with acute agitation associated with schizophrenia in a real-world clinical setting. Methods: The postmarketing surveillance study with a 3-day observational period after the last RAIM administration was conducted (original study. Following this, an extended study was added for patients who received oral olanzapine after RAIM administration during the original study period, in order to additionally observe them for 7 days after initial RAIM administration. Effectiveness and safety from initial RAIM administration were evaluated using the Positive and Negative Syndrome Scale-Excited Component score and treatment-emergent adverse events (TEAEs, respectively. Results: The effectiveness and safety analysis set included a total of 521 and 522 patients, respectively. A majority of patients received 10 mg of RAIM (475/522 patients, 91.0%. The mean ± SD total Positive and Negative Syndrome Scale-Excited Component score was 23.6±6.2 (n=318 at baseline (before initial RAIM administration, 17.4±6.8 (n=280 at 2 hours after initial administration, 16.2±6.8 (n=246 2 days after final administration, 14.9±6.2 (n=248 3 days after final administration, 13.8±5.9 (n=242 4 days after final administration, 13.2±5.8 (n=221 7 days after initial

  1. Switching to olanzapine long-acting injection from either oral olanzapine or any other antipsychotic: comparative post hoc analyses

    Directory of Open Access Journals (Sweden)

    Ciudad A

    2013-11-01

    Full Text Available Antonio Ciudad,1 Ernie Anand,2 Lovisa Berggren,3 Marta Casillas,4 Alexander Schacht,3 Elena Perrin5 1Department of Clinical Research and Development, Eli Lilly & Co, Madrid, Spain; 2Neuroscience Medical Affairs – EU, Lilly Research Centre, Windlesham, Surrey, UK; 3Global Statistical Sciences, Eli Lilly & Co, Bad Homburg, Germany; 4European Scientific Communications, Eli Lilly & Co, Madrid, Spain; 5Medical Department, Eli Lilly & Co, Suresnes, Paris, France Background: A considerable proportion of patients suffering from schizophrenia show suboptimal responses to oral antipsychotics due to inadequate adherence. Hence, they are likely to benefit from switching to a long-acting injectable formulation. These post hoc analyses assessed the clinical effects of switching to olanzapine long-acting injection (OLAI from either oral olanzapine (OLZ or other antipsychotics (non-OLZ. Methods: Post hoc analyses were done based on two randomized studies (one short-term, one long-term conducted in patients suffering from schizophrenia and treated with OLAI. The short-term study was an 8-week placebo-controlled, double-blind trial in acute patients, and the long-term study was a 2-year, oral olanzapine-controlled, open-label, follow-up of stabilized outpatients. Results: These analyses used data from 62 OLAI-treated patients (12 switched from OLZ, 50 from non-OLZ from the short-term study and 190 OLAI-treated patients (56 switched from OLZ, 134 from non-OLZ from the long-term study. Kaplan–Meier survival analyses of time to all-cause discontinuation of OLAI treatment did not differ significantly between OLZ and non-OLZ patients in the short-term study (P=0.209 or long-term study (P=0.448. Similarly, the proportions of OLZ and non-OLZ patients that discontinued OLAI were not statistically different in the short-term (16.7% versus 36.0%, respectively; P=0.198 or long-term (57.1% versus 47.8% respectively; P=0.238 studies. In the short-term study, no

  2. Factors associated with early response to olanzapine and clinical and functional outcomes of early responders treated for schizophrenia in the People’s Republic of China

    Directory of Open Access Journals (Sweden)

    Ye W

    2014-05-01

    Full Text Available Wenyu Ye,1 William Montgomery,2 Zbigniew Kadziola,3 Li Liu,4 Haibo Xue,4 Michael D Stensland,5 Tamas Treuer61Real World Analytics, Eli Lilly and Company, Indianapolis, IN, USA; 2Global Patient Outcomes and Real World Evidence, Eli Lilly Australia Pty Ltd, West Ryde, Australia; 3Real World Analytics Capabilities, Eli Lilly GmbH, Vienna, Austria; 4Lilly Suzhou Pharmaceutical Co, Ltd, Shanghai Branch, People’s Republic of China; 5Agile Outcomes Research, Inc., Rochester, MN, USA; 6Neuroscience Research, Eli Lilly and Company, Budapest, HungaryBackground: The aims of this analysis were to identify factors associated with early response (at 4 weeks to olanzapine treatment and to assess whether early response is associated with better longer-term outcomes for patients with schizophrenia in the People’s Republic of China.Methods: A post hoc analysis of a multi-country, 6-month, prospective, observational study of outpatients with schizophrenia or bipolar mania who initiated or switched to treatment with oral olanzapine was conducted using data from the Chinese schizophrenia subgroup (n=330. Factors associated with early response were identified using a stepwise logistic regression with baseline clinical characteristics, baseline participation in a weight control program, and adherence with antipsychotics during the first 4 weeks of treatment. Mixed models for repeated measures with baseline covariates were used to compare outcomes over time between early responders and early nonresponders to olanzapine.Results: One hundred and thirty patients (40% achieved an early response. Early response was independently predicted by higher baseline Clinical Global Impressions-Severity score (odds ratio [OR] 1.51, 95% confidence interval [CI] 1.15–1.97, fewer years since first diagnosis (OR 0.94, CI 0.90–0.98, a greater number of social activities (OR 1.22, CI 1.05–1.40, participation in a weight control program (OR 1.81, CI 1.04–3.15, and high adherence

  3. Ketamine: stimulating antidepressant treatment?

    Science.gov (United States)

    Malhi, Gin S; Byrow, Yulisha; Cassidy, Frederick; Cipriani, Andrea; Demyttenaere, Koen; Frye, Mark A; Gitlin, Michael; Kennedy, Sidney H; Ketter, Terence A; Lam, Raymond W; McShane, Rupert; Mitchell, Alex J; Ostacher, Michael J; Rizvi, Sakina J; Thase, Michael E; Tohen, Mauricio

    2016-05-01

    The appeal of ketamine - in promptly ameliorating depressive symptoms even in those with non-response - has led to a dramatic increase in its off-label use. Initial promising results await robust corroboration and key questions remain, particularly concerning its long-term administration. It is, therefore, timely to review the opinions of mood disorder experts worldwide pertaining to ketamine's potential as an option for treating depression and provide a synthesis of perspectives - derived from evidence and clinical experience - and to consider strategies for future investigations. G.S.M. Grant/research support: National Health Medical Research Council, NSW Health, Ramsay Health, American Foundation for Suicide Prevention, AstraZeneca, Eli Lilly & Co, Organon, Pfizer, Servier, and Wyeth; has been a speaker for Abbott, AstraZeneca, Eli Lilly & Co, Janssen Cilag, Lundbeck, Pfizer, Ranbaxy, Servier, and Wyeth; consultant: AstraZeneca, Eli Lilly & Co, Janssen Cilag, Lundbeck, and Servier. M.A.F. Grant support: AssureRx, Janssen Research & Development, Mayo Foundation, Myriad, National Institute of Alcohol Abuse and Alcoholism (NIAAA), National Institute of Mental Health (NIMH), Pfizer. Consultant (Mayo): Janssen Research & Development, LLC, Mitsubishi Tanabe Pharma Corporation, Myriad Genetics, Neuralstem Inc., Sunovion, Supernus Pharmaceuticals, Teva Pharmaceuticals. CME/travel support: American Physician Institute, CME Outfitters. Financial interest/Mayo Clinic 2016: AssureRx. S.H.K. Grant/research support: Brain Canada, Bristol Meyer Squibb, CIHR, Janssen, Johnson & Johnson, Lundbeck, Ontario Brain Institute, Pfizer, Servier, St. Jude Medical, Sunovion. T.A.K. Grant/research support (through Stanford University): Sunovion Pharmaceuticals and Merck & Co., Inc.; consultant/advisory board bember: Allergan, Inc., Janssen Pharmaceuticals, Myriad Genetic Laboratories, Inc., and Sunovion Pharmaceuticals; lecture honoraria (not Speaker's Bureau payments): Glaxo

  4. Assessment of direct analgesic effect of duloxetine for chronic low back pain: post hoc path analysis of double-blind, placebo-controlled studies

    Directory of Open Access Journals (Sweden)

    Enomoto H

    2017-06-01

    Full Text Available Hiroyuki Enomoto,1 Shinji Fujikoshi,2 Jumpei Funai,3 Nao Sasaki,4 Michael H Ossipov,5 Toshinaga Tsuji,6 Levent Alev,7 Takahiro Ushida8 1Medical Science, Eli Lilly Japan K.K., Tokyo, 2Statistical Science, 3Science Communications, 4Medical Science, Eli Lilly Japan K.K., Kobe, Japan; 5Clinical Division, inVentiv Health, LLC, Blue Bell, PA, USA; 6Medical Affairs Department, Shionogi & Co., Ltd., Osaka, Japan; 7Medical Department, Lilly Turkey, Istanbul, Turkey; 8Multidisciplinary Pain Center, Aichi Medical University, Nagakute, Aichi, Japan Background: Comorbid depression and depressive symptoms are common in patients with chronic low back pain (CLBP. Duloxetine is clinically effective in major depressive disorder and several chronic pain states, including CLBP. The objective of this post hoc meta-analysis was to assess direct and indirect analgesic efficacy of duloxetine for patients with CLBP in previous clinical trials. Methods: Post hoc path analyses were conducted of 3 randomized, double-blind, clinical studies of patients receiving duloxetine or placebo for CLBP. The primary outcome measure for pain was the Brief Pain Inventory, average pain score. A secondary outcome measure, the Beck Depression Inventory-II, was used for depressive symptoms. The changes in score from baseline to endpoint were determined for each index. Path analyses were employed to calculate the proportion of analgesia that may be attributed to a direct effect of duloxetine on pain.Results: A total of 851 patients (400 duloxetine and 451 placebo were included in this analysis. Duloxetine significantly improved pain scores compared with placebo (p<0.001. It also significantly improved depressive scores compared with placebo (p=0.015. Path analyses showed that 91.1% of the analgesic effect of duloxetine could be attributed to a direct analgesic effect, and 8.9% to its antidepressant effect. Similar results were obtained when data were evaluated at weeks 4 and 7, and when

  5. A review of the efficacy of atomoxetine in the treatment of attention-deficit hyperactivity disorder in children and adult patients with common comorbidities

    Directory of Open Access Journals (Sweden)

    Clemow DB

    2017-02-01

    Full Text Available David B Clemow,1 Chris Bushe,2 Michele Mancini,3 Michael H Ossipov,4 Himanshu Upadhyaya1 1Eli Lilly and Company, Indianapolis, IN, USA; 2Eli Lilly, Windlesham, UK; 3Eli Lilly Italia S.p.A., Sesto Fiorentino, Italy; 4inVentiv Health Clinical, LLC, Blue Bell, PA, USA Abstract: Attention-deficit hyperactivity disorder (ADHD is a common neuropsychiatric disorder that is often diagnosed during childhood, but has also increasingly been recognized to occur in adults. Importantly, up to 52% of children (including adolescents and 87% of adults with ADHD also have a comorbid psychiatric disorder. The presence of a comorbid disorder has the potential to impact diagnosis and could affect treatment outcomes. Atomoxetine is a nonstimulant treatment for ADHD. Despite numerous published studies regarding efficacy of atomoxetine in the treatment of ADHD in patients with comorbid disorders, there is limited information about the impact of individual common comorbid disorders on the efficacy of atomoxetine for ADHD, especially with regard to adults. Moreover, a cumulative review and assessment of these studies has not been conducted. For this reason, we performed a literature review to find, identify, and cumulatively review clinical studies that examined the efficacy of atomoxetine in the treatment of patients with ADHD and comorbid psychiatric disorders. We found a total of 50 clinical studies (37 in children; 13 in adults that examined the efficacy of atomoxetine in patients with ADHD and a comorbid disorder. The comorbidities that were studied in children or in adults included anxiety, depression, and substance use disorder. Overall, the presence of comorbidity did not adversely impact the efficacy of atomoxetine in treatment of ADHD symptoms in both patient populations. In the studies identified and assessed in this review, atomoxetine did not appear to exacerbate any of the comorbid conditions and could, therefore, be an important therapy choice for the

  6. Estimating the real world daily usage and cost for exenatide twice daily and liraglutide in Germany, the Netherlands, and the UK based on volumes dispensed by pharmacies

    Directory of Open Access Journals (Sweden)

    McDonell AL

    2015-01-01

    Full Text Available Amanda L McDonell,1 Urpo Kiiskinen,2 Danielle C Zammit,3 Robert W Kotchie,1 Per-Olof Thuresson,3 Claudia Nicolay,4 Thomas Haslam,1 Michiel Bruinsma,5 Anne-Jeanine Janszen-Van Oosterhout,6 Thorsten Otto41IMS Health, London, UK; 2Eli Lilly and Company, Helsinki, Finland; 3IMS Health, Basel, Switzerland; 4Eli Lilly and Company, Bad Homburg, Germany; 5IMS Health, Rotterdam, the Netherlands; 6Eli Lilly Nederland, Houten, the NetherlandsBackground: Glucagon-like peptide-1 (GLP-1 receptor agonists are indicated for improvement of glycemic control in adults with type 2 diabetes. Cost is one aspect of treatment to be considered, in addition to clinical benefits, when selecting optimal therapy for a patient. The objective of this study was to estimate the average dose usage and real world daily cost of the GLP-1 receptor agonists, exenatide twice daily and liraglutide once daily, in Germany, the Netherlands, and the UK.Methods: Administrative databases were used to source the data from longitudinal records of dispensed prescriptions. Data were extracted from the IMS Longitudinal Prescription database which captures details of prescriptions dispensed in pharmacies. Information on the dispensed quantity of each product was used to estimate average daily usage per patient. Daily dose usage was multiplied by the public price per unit to estimate daily cost.Results: The dispensed volume in Germany corresponded to a mean dispensed daily dose of 16.81 µg for exenatide twice daily and 1.37 mg for liraglutide (mean daily cost €4.02 and €4.54, respectively. In the Netherlands, average dispensed daily doses of 17.07 µg and 1.49 mg were observed for exenatide twice daily and liraglutide (mean daily cost €3.05 and €3.97, respectively. In the UK, the mean dispensed volume corresponded to a daily usage of 20.49 µg for exenatide twice daily and 1.50 mg for liraglutide (mean daily cost £2.53 and £3.28, respectively.Conclusion: Estimates of average daily

  7. Clinical course of nonalcoholic fatty liver disease: an assessment of severity, progression, and outcomes

    Directory of Open Access Journals (Sweden)

    Simeone JC

    2017-12-01

    Full Text Available Jason C Simeone,1 Jay P Bae,2 Byron J Hoogwerf,3 Qian Li,1 Axel Haupt,3 Ayad K Ali,4 Marilyn K Boardman,3 Beth L Nordstrom1 1Real-world Evidence, Evidera, Waltham, MA, USA; 2Global Patient Outcomes and Real World Evidence, Eli Lilly and Company, Indianapolis, IN, USA; 3Lily Diabetes, Eli Lilly and Company, Indianapolis, IN, USA; 4Global Patient Safety, Eli Lilly and Company, Indianapolis, IN, USA Purpose: To identify the characteristics and initial disease severity of patients with nonalcoholic fatty liver disease (NAFLD and assess incidence and risk factors for disease progression in a retrospective study.Methods: Patients ≥18 years of age without alcoholism or other liver diseases (eg, hepatitis B/C were selected from Geisinger Health System electronic medical record data from 2004 to 2015. Initial disease stage was stratified into uncomplicated NAFLD, advanced fibrosis, cirrhosis, hepatocellular carcinoma (HCC, and liver transplant using clinical biomarkers, diagnosis, and procedure codes. Disease progression was defined as stage progression or death and analyzed via Kaplan–Meier plots and multistate models.Results: In the NAFLD cohort (N=18,754, 61.5% were women, 39.0% had type 2 diabetes mellitus (T2DM, and the mean body mass index was 38.2±10.2 kg/m2. At index, 69.9% had uncomplicated NAFLD, 11.7% had advanced fibrosis, and 17.8% had cirrhosis. Of 18,718 patients assessed for progression, 17.3% progressed (11.0% had stage progression, 6.3% died without evidence of stage progression during follow-up (median=842 days. Among subgroups, 12.3% of those without diabetes mellitus progressed vs 24.7% of those with T2DM. One-year mortality increased from 0.5% in uncomplicated NAFLD to 22.7% in HCC. After liver transplant, mortality decreased to 5.6% per year.Conclusions: In 2.3 years of follow-up, approximately 17% of patients progressed or died without evidence of stage progression. T2DM was associated with approximately twice the risk of

  8. Health care costs before and after diagnosis of depression in patients with unexplained pain: a retrospective cohort study using the United Kingdom General Practice Research Database

    Directory of Open Access Journals (Sweden)

    Reed C

    2013-01-01

    Full Text Available Catherine Reed,1 Jihyung Hong,2 Diego Novick,1 Alan Lenox-Smith,3 Michael Happich41Global Health Outcomes, Eli Lilly and Company, Windlesham, Surrey, UK; 2Personal Social Services Research Unit, London School of Economics and Political Science, London, UK; 3Eli Lilly UK, Basingstoke, UK; 4Eli Lilly and Company, Bad Homburg, GermanyPurpose: To assess the impact of pain severity and time to diagnosis of depression on health care costs for primary care patients with pre-existing unexplained pain symptoms who subsequently received a diagnosis of depression.Patients and methods: This retrospective cohort study analyzed 4000 adults with unexplained pain (defined as painful physical symptoms [PPS] without any probable organic cause and a subsequent diagnosis of depression, identified from the UK General Practice Research Database using diagnostic codes. Patients were categorized into four groups based on pain severity (milder or more severe; based on number of pain-relief medications and use of opioids and time to diagnosis of depression (≤1 year or >1 year from PPS index date. Annual health care costs were calculated (2009 values and included general practitioner (GP consultations, secondary care referrals, and prescriptions for pain-relief medications for the 12 months before depression diagnosis and in the subsequent 2 years. Multivariate models of cost included time period as a main independent variable, and adjusted for age, gender, and comorbidities.Results: Total annual health care costs before and after depression diagnosis for the four patient groups were higher for the groups with more severe pain (£819–£988 versus £565–£628; P < 0.001 for all pairwise comparisons and highest for the group with more severe pain and longer time to depression diagnosis in the subsequent 2 years (P < 0.05. Total GP costs were highest in the group with more severe pain and longer time to depression diagnosis both before and after depression diagnosis (P

  9. Generation and characterization of ixekizumab, a humanized monoclonal antibody that neutralizes interleukin-17A

    Directory of Open Access Journals (Sweden)

    Liu L

    2016-04-01

    Full Text Available Ling Liu,1 Jirong Lu,1 Barrett W Allan,2 Ying Tang,2 Jonathan Tetreault,1 Chi-kin Chow,1 Barbra Barmettler,2 James Nelson,2 Holly Bina,1 Lihua Huang,3 Victor J Wroblewski,4 Kristine Kikly1 1Biotechnology Discovery Research, Indianapolis, IN, 2Applied Molecular Evolution, Lilly Biotechnology Center, San Diego, CA, 3Bioproduct Research and Development, 4Drug Disposition, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA Abstract: Interleukin (IL-17A exists as a homodimer (A/A or as a heterodimer (A/F with IL-17F. IL-17A is expressed by a subset of T-cells, called Th17 cells, at inflammatory sites. Most cell types can respond to the local production of IL-17A because of the near ubiquitous expression of IL-17A receptors, IL-17RA and IL-17RC. IL-17A stimulates the release of cytokines and chemokines designed to recruit and activate both neutrophils and memory T-cells to the site of injury or inflammation and maintain a proinflammatory state. IL-17A-producing pathogenic T-cells contribute to the pathogenesis of autoimmune diseases, including psoriasis, psoriatic arthritis, rheumatoid arthritis, and ankylosing spondylitis. This study describes the generation and characterization of ixekizumab, a humanized IgG4 variant IL-17A-neutralizing antibody. Ixekizumab binds human and cynomolgus monkey IL-17A with high affinity and binds rabbit IL-17A weakly but does not bind to rodent IL-17A or other IL-17 family members. Ixekizumab effectively inhibits the interaction between IL-17A and its receptor in binding assays and potently blocks IL-17A-induced GRO or KC secretion in cell-based assays. In an in vivo mouse pharmcodynamic model, ixekizumab blocks human IL-17A-induced mouse KC secretion. These data provide a comprehensive preclinical characterization of ixekizumab, for which the efficacy and safety have been demonstrated in human clinical trials in psoriasis and psoriatic arthritis.Keywords: ixekizumab, IL-17A monoclonal antibody

  10. Clinical response and hospital costs associated with the empirical use of vancomycin and linezolid for hospital-acquired pneumonia in a Chinese tertiary care hospital: a retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Song Y

    2014-10-01

    Full Text Available Yuanlin Song,1,* Yicheng Yang,2,* Wendong Chen,3,4 Wei Liu,2 Kai Wang,2 Xuehai Li,5 Ke Wang,2 Manny Papadimitropoulos,3,6 William Montgomery7 1Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, 2Lilly Suzhou Pharmaceutical Co, Ltd, Shanghai Branch, Shanghai, People's Republic of China; 3Division of Social and Administrative Pharmacy, Leslie Dan Faculty of Pharmacy, University of Toronto, 4Normin Health, Toronto, ON, Canada; 5VitalStrategic Research Institute, Shanghai, People's Republic of China; 6Global Health Outcomes Research, Eli Lilly, Indianapolis, IN, USA; 7Eli Lilly Australia Pty Ltd, West Ryde, NSW, Australia *These authors contributed equally to this work Aims: To evaluate clinical outcomes and allocation of hospital costs associated with empirical use of vancomycin or linezolid for hospital-acquired pneumonia (HAP in the People's Republic of China. Methods: Hospital episodes including HAP treated by vancomycin or linezolid between 2008 and 2012 in a Chinese tertiary care hospital were retrospectively identified from hospital administrative databases. Propensity score methods created best-matched pairs for the antibiotics. The matched pairs were used for adjusted comparisons on clinical response and allocation of hospital costs. Multiple regression analyses adjusting residual imbalance after matching were performed to confirm adjusted comparisons. Results: Sixty matched pairs were created. Adjusted comparisons between vancomycin and linezolid showed similar clinical response rates (clinical cure: 30.0% versus 31.7%, respectively; P=0.847; treatment failure: 55.0% versus 45.0%, respectively; P=0.289 but a significantly lower in-hospital mortality rate for vancomycin (3.3% versus 18.3%, respectively; P=0.013. After further adjusting for the imbalanced variables between matched treatment groups, the risks of treatment failure associated with the two antibiotics were comparable (odds ratio: 1.139; P=0.308 and there was

  11. Sex differences in the course of schizophrenia across diverse regions of the world

    Directory of Open Access Journals (Sweden)

    Novick D

    2016-11-01

    Full Text Available Diego Novick,1 William Montgomery,2 Tamas Treuer,3 Maria Victoria Moneta,4 Josep Maria Haro4 1Eli Lilly and Company, Windlesham, Surrey, UK; 2Eli Lilly Australia Pty Ltd, West Ryde, NSW, Australia; 3Eli Lilly and Company, Neuroscience Research, Budapest, Hungary; 4Parc Sanitari Sant Joan de Déu, CIBERSAM, Universitat de Barcelona, Barcelona, Spain Abstract: This study explores sex differences in the outcomes of patients with schizophrenia (clinical/functional remission and recovery across diverse regions of the world (Northern Europe, Southern Europe, Central and Eastern Europe, Latin America, East Asia, and North Africa and the Middle East. Data (n=16,380 for this post hoc analysis were taken from the World-Schizophrenia Health Outcomes Study. In most regions, females had a later age at first service contact for schizophrenia, a lower level of overall/negative symptom severity, lower rates of alcohol/substance abuse and paid employment, and higher percentages of having a spouse/partner and independent living. Overall, females had slightly higher rates of clinical remission (58.0% vs 51.8%, functional remission (22.8% vs 16.0%, and recovery (16.5% vs 16.0% at 36 months (P<0.001 for all. This pattern was consistently observed in Southern Europe and Northern Europe even after controlling for baseline sex differences, but not in other regions. In Central and Eastern Europe, rates of clinical remission were higher in females at 36 months, but those of functional remission and recovery were similar between males and females. The opposite was observed for Latin America. In East Asia, sex differences were rarely observed for these outcomes. Finally, in North Africa and the Middle East, sex differences in these outcomes were pronounced only in regression analyses. These regional variations shed light on the importance of psychosocial and cultural factors and their effects on sex in the prognosis of schizophrenia. Keywords: sex, remission, recovery

  12. A cost-effectiveness analysis of first-line induction and maintenance treatment sequences in patients with advanced nonsquamous non-small-cell lung cancer in France

    Directory of Open Access Journals (Sweden)

    Taipale K

    2017-08-01

    Full Text Available Kaisa Taipale,1 Katherine B Winfree,2 Mark Boye,2 Mickael Basson,3 Ghassan Sleilaty,4 James Eaton,5 Rachel Evans,5 Christos Chouaid6 1Global Patient Outcomes and Real World Evidence International, Oy Eli Lilly Finland AB, Helsinki, Finland; 2Global Patient Outcomes and Real World Evidence, Eli Lilly and Company, Indianapolis, IN, USA; 3Corporate Affairs, Lilly France, Neuilly-sur-Seine, 4Bio-Medicines Medical Affairs, Lilly France, Neuilly-sur-Seine, France; 5ICON Health Economics and Epidemiology, ICON Plc, Milton Park, UK; 6Thoracic Oncology, Service de Pneumologie, Centre Hospitalier Intercommunal Créteil, Créteil, France Background: Comparative effectiveness and cost-effectiveness data for induction–maintenance (I–M sequences for the treatment of patients with nonsquamous non-small-cell lung cancer (nsqNSCLC are limited because of a lack of direct evidence. This analysis aimed to compare the cost-effectiveness of I–M pemetrexed with those of other I–M regimens used for the treatment of patients with advanced nsqNSCLC in the French health-care setting. Materials and methods: A previously developed global partitioned survival model was adapted to the France-only setting by restricting treatment sequences to include 12 I–M regimens most relevant to France, and incorporating French costs and resource-use data. Following a systematic literature review, network meta-analyses were performed to obtain hazard ratios for progression-free survival (PFS and overall survival (OS relative to gemcitabine + cisplatin (induction sequences or best supportive care (BSC (maintenance sequences. Modeled health-care benefits were expressed as life-years (LYs and quality-adjusted LYs (QALYs (estimated using French EuroQol five-dimension questionnaire tariffs. The study was conducted from the payer perspective (National Health Insurance. Cost- and benefit-model inputs were discounted at an annual rate of 4%. Results: Base-case results showed pemetrexed

  13. The industrial application requirement for biotech inventions in light of recent EPO & UK case law:

    DEFF Research Database (Denmark)

    Minssen, Timo; Nilsson, David

    2012-01-01

    In this study we illuminate and discuss the most recent developments in respect of the interpretation of the “industrial application” requirement with respect to gene and protein related inventions in Europe. The analysis will focus on the relevant provisions of the EPC and decisional practice from...... the European Patent Organisation (“EPO”), particularly decisions from the Technical Board of Appeal 3.3.08 (the “Board”). To get a glimpse of the national dimension, we will also look at the first patent judgment from the "new" UK Supreme Court, i.e. the groundbreaking decision in HGS v Eli Lilly, In the final...... discussion, we will elaborate on two issues in particular; (i) determine which types of qualities an invention should have in order to meet the industrial application requirement in the first place; and (ii) what type of evidence an applicant is expected to present in respect of (potential) applications...

  14. The insulin secretory action of novel polycyclic guanidines: discovery through open innovation phenotypic screening, and exploration of structure-activity relationships.

    Science.gov (United States)

    Shaghafi, Michael B; Barrett, David G; Willard, Francis S; Overman, Larry E

    2014-02-15

    We report the discovery of the glucose-dependent insulin secretogogue activity of a novel class of polycyclic guanidines through phenotypic screening as part of the Lilly Open Innovation Drug Discovery platform. Three compounds from the University of California, Irvine, 1-3, having the 3-arylhexahydropyrrolo[1,2-c]pyrimidin-1-amine scaffold acted as insulin secretagogues under high, but not low, glucose conditions. Exploration of the structure-activity relationship around the scaffold demonstrated the key role of the guanidine moiety, as well as the importance of two lipophilic regions, and led to the identification of 9h, which stimulated insulin secretion in isolated rat pancreatic islets in a glucose-dependent manner. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Measuring the effectiveness and impact of an open innovation platform.

    Science.gov (United States)

    Carroll, Glenn P; Srivastava, Sanjay; Volini, Adam S; Piñeiro-Núñez, Marta M; Vetman, Tatiana

    2017-05-01

    Today, most pharmaceutical companies complement their traditional R&D models with some variation on the Open Innovation (OI) approach in an effort to better access global scientific talent, ideas and hypotheses. Traditional performance indicators that measure economic returns from R&D through commercialization are often not applicable to the practical assessment of these OI approaches, particularly within the context of early drug discovery. This leaves OI programs focused on early R&D without a standard assessment framework from which to evaluate overall performance. This paper proposes a practical dashboard for such assessment, encompassing quantitative and qualitative elements, to enable decision-making and improvement of future performance. The use of this dashboard is illustrated using real-time data from the Lilly Open Innovation Drug Discovery (OIDD) program. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  16. Cardiovascular Side Effects of Atomoxetine and Its Interactions with Inhibitors of the Cytochrome P450 System

    Directory of Open Access Journals (Sweden)

    Pashtoon Murtaza Kasi

    2011-01-01

    Full Text Available Attention deficit hyperactivity disorder (ADHD is one of the most common neurobehavioral disorders of childhood and adolescence. Classically, stimulants have been used in the treatment of this condition. Atomoxetine (Strattera; Eli Lilly and Company is a selective norepinephrine reuptake inhibitor (SNRI, one of the first medications in the nonstimulant class of medications that has been approved by the FDA for the treatment of ADHD. Atomoxetine is a phenoxypropylamine derivative and is structurally related to the antidepressant fluoxetine. The common side effects reported with the use of atomoxetine include mainly GI disturbances. Cardiovascular side effects are less commonly reported. The increase in the noradrenergic tone may explain some of the side effects noted with the use of this medication. Here, we present a case of a patient who presented with syncope, orthostatic hypotension, and tachycardia and discuss the various clinical implications based on the pharmacokinetics and pharmacodynamics of the drug.

  17. Deposito Diademate: Augustine’s Emperors

    Directory of Open Access Journals (Sweden)

    Peter Iver Kaufman

    2015-03-01

    Full Text Available To assist colleagues from other disciplines who teach Augustine’s texts in their core courses, this contribution to the Lilly Colloquium discusses Augustine’s assessments of Emperors Constantine and Theodosius. His presentations of their tenure in office and their virtues suggest that his position on political leadership corresponds with his general skepticism about political platforms and platitudes. Yet careful reading of his revision of Ambrose’s account of Emperor Theodosius’s public penance and reconsideration of the last five sections of his fifth book City of God—as well as a reappraisal of several of his sermons on the Psalms—suggest that he proposes a radical alternative to political conformity relevant to undergraduates’ conventional expectations of society’s progress and their parts in it.

  18. Patent border wars: defining the boundary between scientific discoveries and patentable inventions.

    Science.gov (United States)

    Holman, Christopher M

    2007-12-01

    Drawing an appropriate boundary between unpatentable natural phenomena and patentable inventions is crucial in preventing the patent laws from unduly restricting access to fundamental scientific discoveries. Some would argue that, particularly in the U.S., patents are being issued that purport to claim a novel product or process but that, in effect, encompass any practical application of a fundamental biological principle. Examples include gene patents, which Congress is considering banning, and patents relating to biological correlations and pathways, such as the patents at issue in the headline-grabbing LabCorp v. Metabolite and Ariad v. Eli Lilly litigations. In view of the mounting concern, it seems likely that Congress and/or the courts will address the issue, and perhaps substantially shift the boundary.

  19. Inhaled insulin for controlling blood glucose in patients with diabetes

    Directory of Open Access Journals (Sweden)

    Bernard L Silverman

    2008-01-01

    Full Text Available Bernard L Silverman1, Christopher J Barnes2, Barbara N Campaigne3, Douglas B Muchmore31Alkermes, Inc, Cambridge, MA, USA; 2i3 Statprobe, Ann Arbor, MI; 3Eli Lilly and Company, Indianapolis, IN, USAAbstract: Diabetes mellitus is a significant worldwide health problem, with the incidence of type 2 diabetes increasing at alarming rates. Insulin resistance and dysregulated blood glucose control are established risk factors for microvascular complications and cardiovascular disease. Despite the recognition of diabetes as a major health issue and the availability of a growing number of medications designed to counteract its detrimental effects, real and perceived barriers remain that prevent patients from achieving optimal blood glucose control. The development and utilization of inhaled insulin as a novel insulin delivery system may positively influence patient treatment adherence and optimal glycemic control, potentially leading to a reduction in cardiovascular complications in patients with diabetes.Keywords: diabetes, inhaled insulin, cardiovascular disease, blood glucose

  20. An industry update: the latest news in therapeutic delivery.

    Science.gov (United States)

    Harris, Elaine

    2017-11-01

    The present industry update covers the period 1-31 July 2017. Information was sourced primarily from company press releases, regulatory and patent agencies, scientific literature and various news websites. There was positive approval news this month for GlaxoSmithKline for its new self-injecting treatment for systemic lupus erythematosus but less positive news for Ocular Therapeutix, a new drug application for its treatment for postoperative ocular pain, DEXTENZA™ was rejected for a second time. Endo Pharmaceuticals agreed to withdraw its opioid formulation Opana ® Er due to abuse concerns. Collaborations for novel therapeutic delivery research were announced this month by Takeda and BioSurfaces, Catelent and Rutgers University, Lilly and Purdue University and Titan Pharmaceuticals with Walter Reed and the Southwest Research Institute. A number of companies announced significant financing deals to allow for the clinical development of products with enhanced delivery options including Sebacia and Diasome.

  1. Resource use and costs of exenatide bid or insulin in clinical practice: the European CHOICE study

    Directory of Open Access Journals (Sweden)

    Kiiskinen U

    2013-07-01

    Full Text Available Urpo Kiiskinen,1 Stephan Matthaei,2 Matthew Reaney,3 Chantal Mathieu,4 Claes-Göran Östenson,5 Thure Krarup,6 Michael Theodorakis,7,* Jacek Kiljanski,8 Carole Salaun-Martin,9 Hélène Sapin,9 Bruno Guerci10 1Eli Lilly, Helsinki, Finland; 2Quakenbrück Diabetes Center, Quakenbrück, Germany; 3Eli Lilly, Windlesham, Surrey, UK; 4Department of Endocrinology, UZ Gasthuisberg, Leuven, Belgium; 5Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; 6Department of Endocrinology, Bispebjerg Hospital, Copenhagen, Denmark; 7Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece; 8Eli Lilly, Warsaw, Poland; 9Eli Lilly, Neuilly Cedex, France; 10Department of Diabetes, Metabolic Diseases, and Nutrition, Hôpital Brabois, Vandoeuvre-Lès-Nancy, France *Michael Theodorakis was affiliated with the institution shown above at the time of the study, but has since left this institution Purpose: CHOICE (CHanges to treatment and Outcomes in patients with type 2 diabetes initiating InjeCtablE therapy assessed patterns of exenatide bid and initial insulin therapy usage in clinical practice in six European countries and evaluated outcomes during the study. Methods: CHOICE was a 24-month, prospective, noninterventional observational study. Clinical and resource use data were collected at initiation of first injectable therapy (exenatide bid or insulin and at regular intervals for 24 months. Costs were evaluated from the national health care system perspective at 2009 prices. Results: A total of 2515 patients were recruited. At the 24-month analysis, significant treatment change had occurred during the study in 42.2% of 1114 eligible patients in the exenatide bid cohort and 36.0% of 1274 eligible patients in the insulin cohort. Improvements in glycemic control were observed over the course of the study in both cohorts (P < 0.001 for both, but mean weight was reduced in the exenatide bid cohort (P < 0

  2. Treatment outcomes after initiation of exenatide twice daily or insulin in clinical practice: 12-month results from CHOICE in six European countries

    Directory of Open Access Journals (Sweden)

    Ostenson CG

    2013-04-01

    Full Text Available Claes-Göran Östenson,1 Stephan Matthaei,2 Matthew Reaney,3 Thure Krarup,4 Bruno Guerci,5 Jacek Kiljanski,6 Carole Salaun-Martin,7 Hélène Sapin,7 David Bruhn,8 Chantal Mathieu,9 Michael Theodorakis10 1Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden; 2Diabetes-Center Quakenbrück, Quakenbrück, Germany; 3Eli Lilly, Windlesham, Surrey, UK; 4Department of Endocrinology I, Bispebjerg Hospital, Copenhagen, Denmark; 5Diabetology, Metabolic Diseases and Nutrition, Brabois Hospital, CHU Nancy, and INSERM CIC, ILCV, Vandoeuvre Lès Nancy, France; 6Eli Lilly, Warsaw, Poland; 7Eli Lilly, Neuilly Cedex, France; 8Eli Lilly, San Diego, California, USA; 9Department of Endocrinology, UZ Gasthuisberg, Leuven, Belgium; 10Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece* *Michael Theodorakis was affiliated with the institution shown at the time of the study, but has since left this institution Objective: The CHanges to treatment and Outcomes in patients with type 2 diabetes initiating InjeCtablE therapy (CHOICE study assessed time to, and reasons for, significant treatment change after patients with type 2 diabetes (T2DM initiated their first injectable glucose-lowering therapy (exenatide twice daily [BID] or insulin in routine clinical practice, and these patients’ clinical outcomes, in six European countries. This paper reports interim data from the first 12 months of the study. Research design and methods: CHOICE (NCT00635492 is a prospective, noninterventional, observational study. Clinical data were collected at initiation of first injectable therapy and after approximately 3, 6, and 12 months. Results: Of 2497 patients enrolled in CHOICE, 1096 in the exenatide BID and 1239 in the insulin cohorts had ≥1 post-baseline assessment and were included in this analysis. Overall, 32.2% of the exenatide BID cohort and 29.1% of the insulin cohort (Kaplan–Meier estimates had

  3. Treatment-completion rates with olanzapine long-acting injection versus risperidone long-acting injection in a 12-month, open-label treatment of schizophrenia: indirect, exploratory comparisons

    Directory of Open Access Journals (Sweden)

    Ascher-Svanum H

    2012-05-01

    Full Text Available Haya Ascher-Svanum1, William S Montgomery2, David P McDonnell3, Kristina A Coleman4, Peter D Feldman11Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA; 2Eli Lilly Australia Pty Ltd, West Ryde, New South Wales, Australia; 3Eli Lilly and Company, Cork, Ireland; 4OptumInsight, Lilyfield, New South Wales, AustraliaBackground: Little is known about the comparative effectiveness of atypical antipsychotics in long-acting injection formulation. Due to the absence of head-to-head studies comparing olanzapine long-acting injection and risperidone long-acting injection, this study was intended to make exploratory, indirect, cross-study comparisons between the long-acting formulations of these two atypical antipsychotics in their effectiveness in treating patients with schizophrenia.Methods: Indirect, cross-study comparisons between olanzapine long-acting injection and risperidone long-acting injection used 12-month treatment-completion rates, because discontinuation of an antipsychotic for any cause is a recognized proxy measure of the medication's effectiveness in treating schizophrenia. Following a systematic review of the literature, two indirect comparisons were conducted using open-label, single-cohort studies in which subjects were stabilized on an antipsychotic medication before depot initiation. The first analysis compared olanzapine long-acting injection (one study with pooled data from nine identified risperidone long-acting injection studies. The second analysis was a “sensitivity analysis,” using only the most similar studies, one for olanzapine long-acting injection and one for risperidone long-acting injection, which shared near-identical study designs and involved study cohorts with near-identical patient characteristics. Pearson Chi-square tests assessed group differences on treatment-completion rates.Results: Comparison of olanzapine long-acting injection data (931 patients with the pooled data from the nine

  4. Tikutõmbeid kottpimedas galeriis = Striking matches in a pitch-dark gallery : [luuletused] / Artur Alliksaar

    Index Scriptorium Estoniae

    Alliksaar, Artur, 1923-1966

    2001-01-01

    Tekst eesti ja inglise k. A. Alliksaare lühibiograafia eesti ja inglise k. lk. 55. Sisu: Tikutõmbeid kottpimedas galeriis = Striking matches in a pitch-dark gallery ; "Olen määratusuur mets..." = "I am infinitely vast forest..." ; "Olen koredate külgedega kalju..." = "I am rough-sided cliff..." ; "Olen meri, millel puudub äär..." = "I am sea that knows no bounds..." ; "Liikumine on niivõrd liitunud mu loomusega..." = "Movement is so much part of me..." ; "Ma ei söandaks öelda, et olen rikas..." = "I would not claim that I am rich..." ; Pöördehetk = Turning point ; Kuigi on nii palju lilli... = Though there are so many flowers ; Antidolorosum

  5. An observational study of duloxetine versus SSRI monotherapy for the treatment of painful physical symptoms in Japanese patients with major depressive disorder: primary analysis

    Directory of Open Access Journals (Sweden)

    Kuga A

    2017-08-01

    Full Text Available Atsushi Kuga,1 Toshinaga Tsuji,2 Shinji Hayashi,2 Mako Matsubara,3 Shinji Fujikoshi,4 Hirofumi Tokuoka,1 Aki Yoshikawa,5 Rodrigo Escobar,6 Kazuhide Tanaka,7 Takaharu Azekawa8 1Bio Medicine, Medicines Development Unit Japan, Eli Lilly Japan K.K., Kobe, Japan; 2Medical Affairs Department, Shionogi & Co. Ltd, Osaka, Japan; 3Pharmacovigilance Department, Shionogi & Co. Ltd, Osaka, Japan; 4Statistical Science, Medicines Development Unit Japan, Eli Lilly Japan K.K., Kobe, Japan; 5Scientific Communications, Medicines Development Unit Japan, Eli Lilly Japan K.K. Kobe, Japan; 6Bio-Medicines, Eli Lilly and Company, Indianapolis, IN, USA; 7Hitsuji Clinic, Kusatsu, Japan; 8Shioiri Mental Clinic, Yokosuka, Japan Objective: The objective of this study was to assess the effectiveness of duloxetine monotherapy, in comparison with selective serotonin reuptake inhibitor (SSRI monotherapy, in the treatment of painful physical symptoms (PPS in Japanese patients with major depressive disorder (MDD in real-world clinical settings.Methods: This was a multicenter, 12-week prospective, observational study. This study enrolled MDD patients with at least moderate PPS, defined as a Brief Pain Inventory-Short Form (BPI-SF average pain score (item 5 ≥3. Patients were treated with duloxetine or SSRIs (escitalopram, sertraline, paroxetine, or fluvoxamine for 12 weeks, and PPS were assessed by BPI-SF average pain score. The primary outcome was early improvement in the BPI-SF average pain score at 4 weeks post-baseline. Results: A total of 523 patients were evaluated for treatment effectiveness (duloxetine N=273, SSRIs N=250. The difference in BPI-SF average pain score between the two groups was not statistically significant at 4 weeks post-baseline, the primary endpoint (least-squares mean change from baseline [95% confidence interval]: duloxetine,−2.8 [−3.1, −2.6]; SSRIs, −2.5 [−2.8, −2.3]; P=0.166. There was a numerical advantage for duloxetine in improvement

  6. Humalog(®) KwikPen™: an insulin-injecting pen designed for ease of use.

    Science.gov (United States)

    Schwartz, Sherwyn L; Ignaut, Debra A; Bodie, Jennifer N

    2010-11-01

    Insulin pens offer significant benefits over vial and syringe injections for patients with diabetes who require insulin therapy. Insulin pens are more discreet, easier for patients to hold and inject, and provide better dosing accuracy than vial and syringe injections. The Humalog(®) KwikPen™ (prefilled insulin lispro [Humalog] pen, Eli Lilly and Company, Indianapolis, IN, USA) is a prefilled insulin pen highly rated by patients for ease of use in injections, and has been preferred by patients to both a comparable insulin pen and to vial and syringe injections in comparator studies. Together with an engineering study demonstrating smoother injections and reduced dosing error versus a comparator pen, recent evidence demonstrates the Humalog KwikPen device is an accurate, easy-to-use, patient-preferred insulin pen.

  7. Inversion of Gravity and Magnetic Field Data for Tyrrhena Patera

    Science.gov (United States)

    Milbury, C.; Schubert, G.; Raymond, C. A.; Smrekar, S. E.

    2011-01-01

    Tyrrhena Patera is located to the southeast/northeast of the Isidis/Hellas impact basin. It was geologically active into the Late Amazonian, although the main edifice was formed in the Noachian(approximately 3.7-4.0 Ga). Tyrrhena Patera and the surrounding area contain gravity and magnetic anomalies that appear to be correlated. The results presented here are for the anomalies 1a and 1b (closest to Tyrrhena Patera), however other anomalies in this region have been modeled and will be presented at the conference.The Mars Global Surveyor (MGS) free-air gravity signature of Tyrrhena Patera has been studied by Kiefer, who inferred the existence of an extinct magma chamber below it. The magnetic signature has been mapped by Lillis R. J. et al., who compared electron reflectometer data, analogous to the total magnetic field, for Syrtis Major and Tyrrhena Patera and argued for demagnetization of both volcanoes.

  8. THE EFFECTS OF PANTOTHENIC ACID ON RESPIRATORY ACTIVITY.

    Science.gov (United States)

    Pratt, E F; Williams, R J

    1939-05-20

    Experiments using the Warburg-Barcroft apparatus led to the following results and conclusions: (1) Two yeasts in three different media were strikingly stimulated in their respiration by minute amounts of pantothenic acid. (2) Nine other compounds (vitamins and other biologically important substances) were tested and found in all cases to have on the deficient G.M. yeast, lesser and in some cases no appreciable stimulative effect. Thiamin was the most effective of these compounds. Its action was shown to be different and in some ways antagonistic to that of pantothenic acid. (3) Liver extract (Lilly's Number 343) contains substances capable of speeding up respiration (and growth) to a much higher level than seems possible with known compounds. (4) Pantothenic acid was found to have a definite stimulative effect on fermentation by dialyzed maceration juice from yeast. (5) It likewise stimulated respiration of apple and potato tissue and indications of a similar effect on certain animal tissues were obtained.

  9. Patents, antibiotics, and autarky in Spain.

    Science.gov (United States)

    Romero De Pablos, Ana

    2014-01-01

    Patents on antibiotics were introduced in Spain in 1949. Preliminary research reveals diversification in the types of antibiotics: patents relating to penicillin were followed by those relating to streptomycin, erythromycin and tetracycline. There was also diversification in the firms that applied for patents: while Merck & Co. Incorporated and Schenley Industries Inc. were the main partners with Spanish antibiotics manufacturers in the late 1940s, this industrial space also included many others, such as Eli Lilly & Company, Abbott Laboratories, Chas. Pfizer & Co. Incorporated, and American Cyanamid Company in the mid-1970s. The introduction of these drugs in Spain adds new elements to a re-evaluation of the autarkic politics of the early years of the Franco dictatorship.

  10. Numerical study on turbulent flow inside a channel with an extended chamber

    International Nuclear Information System (INIS)

    Lee, Young Tae; Lim, Hee Chang

    2009-01-01

    The paper presents a LES numerical simulation of turbulent flow around an extended chamber. The simulations are carried out on a series of 3-dimensional cavities placed in a turbulent boundary layer at a Reynolds number of 1.0x10 5 based on U and h, which are the velocity at the upper top of the cavity and the depth height, respectively. In order to get an appropriate solution in the Filtered Navier-Stokes equation for the incompressible flow, the computational mesh is densely attracted to the cavity surface and coarsely far-field, as this aids saving the computation cost and rapid convergence. The Boussinesq hypothesis is employed in the subgrid-scale turbulence model. In order to obtain the subgrid-scale turbulent viscosity, the Smagorinsky-Lilly SGS model is applied and the CFL number for time marching is 1.0. The results include the flow variations inside a cavity with the different sizes and shapes.

  11. Numerical Study on Turbulent Flow Inside a Channel with an Extended Chamber

    International Nuclear Information System (INIS)

    Lee, Young Tae; Lim, Hee Chang

    2010-01-01

    The paper describes a Large Eddy Simulation (LES) study of turbulent flow around a cavity. A series of three-dimensional cavities placed in a turbulent boundary layer are simulated at a Reynolds number of 1.0 x 10 5 by considering U and h, which represent the velocity at the top and the depth of the cavity, respectively. In order to obtain the appropriate solution for the filtered Navier-Stokes equation for incompressible flow, the computational mesh forms dense close to the wall of the cavity but relatively coarse away from the wall; this helps reduce computation cost and ensure rapid convergence. The Boussinesq hypothesis is employed in the subgrid-scale turbulence model. In order to determine the subgrid-scale turbulent viscosity, the Smagorinsky-Lilly SGS model is applied and the CFL number for time marching is set as 1.0. The results show the flow variations inside cavities of different sizes and shapes

  12. Functioning in patients with major depression treated with duloxetine or a selective serotonin reuptake inhibitor in East Asia

    Directory of Open Access Journals (Sweden)

    Novick D

    2016-02-01

    Full Text Available Diego Novick,1 William Montgomery,2 Josep Maria Haro,3 Maria Victoria Moneta,3 Gang Zhu,4 Li Yue,5 Jihyung Hong,6 Héctor Dueñas,7 Roberto Brugnoli8 1Eli Lilly and Company, Windlesham, Surrey, UK; 2Eli Lilly Australia Pty Ltd, West Ryde, NSW, Australia; 3Parc Sanitari Sant Joan de Déu, Fundació Sant Joan de Déu, CIBERSAM, Universitat de Barcelona, Barcelona, Spain; 4Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, 5Lilly Suzhou Pharmaceutical Company, Ltd, Shanghai, People’s Republic of China; 6Department of Healthcare Management, Gachon University, Seongnam, South Korea; 7Eli Lilly de Mexico, Mexico City, Mexico; 8School of Medicine, Sapienza University of Rome, Rome, ItalyPurpose: To assess and compare the levels of functioning in patients with major depressive disorder treated with either duloxetine with a daily dose of ≤60 mg or a selective serotonin reuptake inhibitor (SSRI as monotherapy for up to 6 months in a naturalistic setting in East Asia. In addition, this study examined the impact of painful physical symptoms (PPS on the effects of these treatments.Patients and methods: Data for this post hoc analysis were taken from a 6-month prospective observational study involving 1,549 patients with major depressive disorder without sexual dysfunction. The present analysis focused on a subgroup of patients from East Asia (n=587. Functioning was measured using the Sheehan Disability Scale (SDS. Depression severity was assessed using the 16-item Quick Inventory of Depressive Symptomatology-Self Report. PPS were rated using the modified Somatic Symptom Inventory. A mixed model with repeated measures was fitted to compare the levels of functioning between duloxetine-treated (n=227 and SSRI-treated (n=225 patients, adjusting for baseline patient characteristics.Results: The mean SDS total score was similar between the two treatment cohorts (15.46 [standard deviation =6.11] in the duloxetine

  13. Industrial demand side management: A status report

    Energy Technology Data Exchange (ETDEWEB)

    Hopkins, M.F.; Conger, R.L.; Foley, T.J. [and others

    1995-05-01

    This report provides an overview of and rationale for industrial demand side management (DSM) programs. Benefits and barriers are described, and data from the Manufacturing Energy Consumption Survey are used to estimate potential energy savings in kilowatt hours. The report presents types and examples of programs and explores elements of successful programs. Two in-depth case studies (from Boise Cascade and Eli Lilly and Company) illustrate two types of effective DSM programs. Interviews with staff from state public utility commissions indicate the current thinking about the status and future of industrial DSM programs. A comprehensive bibliography is included, technical assistance programs are listed and described, and a methodology for evaluating potential or actual savings from projects is delineated.

  14. Production of antisera for radioimmunoassay of human proinsulin: preliminary studies

    International Nuclear Information System (INIS)

    Nascimento, M. do; Borghi, V.C.; Bellini, M.H.; Wajchenberg, B.L.

    1990-01-01

    In attempt to the production of anti proinsulin antisera for the radioimmunoassay, five guinea pigs received 50 μg of biosynthetic human proinsulin (Eli Lilly and Company, US) injected subcutaneously. Booster injections were administered at 3 weeks intervals and blood was taken 14 days after the injection. Just after the tenth week, three guinea pigs developed antisera with titers of 1:15.000, 1:1.500 and 1:300 and one of them presented titer lower than 1:300. The evaluation of the specificity of those three antisera showed cross-reactivity only with insulin, which antibodies were not sufficiently sensitive for the assay of endogenous proinsulin from healthy subjects, being only suitable for the measurement of circulating proinsulin in patients with hyper proinsulinemia. Alternative schedules of immunization in order to obtain more sensitive antisera are discussed. (author)

  15. Predictors of remission in the treatment of major depressive disorder: real-world evidence from a 6-month prospective observational study

    Directory of Open Access Journals (Sweden)

    Novick D

    2015-01-01

    Full Text Available Diego Novick,1 Jihyung Hong,1 William Montgomery,2 Héctor Dueñas,3 Magdy Gado,4 Josep Maria Haro5 1Eli Lilly and Company, Windlesham, UK; 2Eli Lilly Australia Pty Ltd, West Ryde, Australia; 3Eli Lilly de Mexico, Mexico City, Mexico; 4Eli Lilly and Company, Riyadh, Saudi Arabia; 5Parc Sanitari Sant Joan de Déu, Fundació Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain Background: This study examined potential predictors of remission among patients treated for major depressive disorder (MDD in a naturalistic clinical setting, mostly in the Middle East, East Asia, and Mexico. Methods: Data for this post hoc analysis were taken from a 6-month prospective, noninterventional, observational study that involved 1,549 MDD patients without sexual dysfunction at baseline in 12 countries worldwide. Depression severity was measured using the Clinical Global Impression of Severity and the 16-item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16. Depression-related pain was measured using the pain-related items of the Somatic Symptom Inventory. Remission was defined as a QIDS-SR16 score ≤5. Generalized estimating equation regression models were used to examine baseline factors associated with remission during follow-up. Results: Being from East Asia (odds ratio [OR] 0.48 versus Mexico; P<0.001, a higher level of depression severity at baseline (OR 0.77, P=0.003, for Clinical Global Impression of Severity; OR 0.92, P<0.001, for QIDS-SR16, more previous MDD episodes (OR 0.92, P=0.007, previous treatments/therapies for depression (OR 0.78, P=0.030, and having any significant psychiatric and medical comorbidity at baseline (OR 0.60, P<0.001 were negatively associated with remission, whereas being male (OR 1.29, P=0.026 and treatment with duloxetine (OR 2.38 versus selective serotonin reuptake inhibitors, P<0.001 were positively associated with remission. However, the association between Somatic Symptom Inventory pain scores

  16. Vegetative Growth of Four Strains of Hericium erinaceus Collected from Different Habitats

    Science.gov (United States)

    Imtiaj, Ahmed; Jayasinghe, Chandana; Lee, Geon Woo; Shim, Mi Ja; Rho, Hyun-Su; Lee, Hyun Sook; Hur, Hyun; Lee, Min Woong; Lee, U-Youn

    2008-01-01

    Vegetative growth of four different strains of Hericium erinaceus was observed. The temperature suitable for optimal mycelial growth was determined to be 25℃, with growth observed in the extend temperature range of 20~30℃. The different strains of this mushroom showed distinct pH requirements for their optimum vegetative growth, with the most favorable growth observed at pH 6. Considering vegetative mycelial growth, PDA, YM, Hennerberg, Hamada, and Glucose peptone were the most favorable media, and Czapek Dox, Hoppkins, Glucose tryptone, and Lilly were the most unfavorable media for these mushroom strains. With the exception of lactose, most of the carbon sources assayed demonstrated favorable vegetative growth of H. erinaceus. For mycelial growth, the most suitable nitrogen source was alanine and the most unsuitable was histidine. Oak sawdust medium supplemented with 10~20% rice bran was the best for mycelial growth of the mushroom. PMID:23990739

  17. Hypoglycemic depression of hepatic phagocytosis in vivo and in the in situ perfused rat liver.

    Science.gov (United States)

    Kober, P M; Filkins, J P

    1981-01-01

    Depression of the phagocytic function of the reticuloendothelial system (RES) during endotoxic hypoglycemia has been implicated in the pathogenesis of endotoxin shock. The present study evaluated the in vivo effects of hypoglycemia on RES function and assessed the effects of an vivo bout of hypoglycemia on phagocytosis in the in situ perfused rat liver. Hypoglycemia was produced in male Holtzman rats using either 1 U of regular insulin (RI) (ILETIN, Lilly) or 0.75 U of long-acting insulin (LAI) (85% LENTE/15% ULTRALENTE, Lilly). RES function was quantitated by intravascular clearance of 8 mg/100 gm body weight colloidal carbon (CC). Two hr after RI and 2.5 hr after LAI, the intravascular halftimes of CC clearance were 19 +/- 2 min (N = 22) and 18 +/- 1 min (N = 19), respectively, as compared to control, 11.3 +/- 0.4 min (N = 53, P less than 0.001). The corresponding plasma glucose (PG) levels were 95 +/- 2 mg/dl in control, 14.4 +/- 0.9 for the RI group, and 17 +/- 1 for LAI. Two hr after RI, livers were perfused for 10 min in situ with 50 mg/liter CC in saline 5% rat serum. PG for control liver donors were 90 +/- 3 mg/dl, while those for hypoglycemic liver donors were 15 +/- 2. CC uptake was decreased from 22 micrograms/min/gm liver in the control (+ serum, n = 19) to 11 +/- 2 in hypoglycemia livers (N = 6); no effect of serum on hypoglycemic depression of the RES was seen. There were no differences in flow rates in the 2 groups. These results indicate that hypoglycemia directly impairs RES function and that the in vivo depression of intravascular clearance is not related to either the presence or absence of serum factors or total hepatic blood flow. Thus, the characteristic hypoglycemia of endotoxin shock may contribute to RES depression and the lethal shock syndrome.

  18. Costs associated with rheumatoid arthritis in Italy: past, present, and future

    Directory of Open Access Journals (Sweden)

    Benucci M

    2016-02-01

    Full Text Available Maurizio Benucci,1 Veronica Rogai,2 Fabiola Atzeni,3 Volker Hammen,4 Piercarlo Sarzti-Puttini,3 Alberto Migliore5 1Rheumatology Unit, S.Giovanni di Dio Hospital, Florence, Italy; 2Eli Lilly Italia SpA, Sesto Fiorentino, Italy; 3Rheumatology Unit, L Sacco Hospital, Milan, Italy; 4Lilly Deutschland GmbH, Bad Homburg, Germany; 5Villa San Pietro Fatebenefratelli Hospital, Rome, Italy Abstract: This literature review examines available evidence on the current and past costs associated with rheumatoid arthritis (RA in Italy, together with the future health-economic prospects for the disease. Studies have been conducted to date on the prevalence, or the associated costs, of RA in Italy. Although future changes in the incidence of RA are a matter of debate, the impact of RA on health care costs is expected to grow in coming decades in line with projected increases in life expectancy and in the proportion of elderly people in Italy. It has been estimated that the indirect (productivity loss and informal care and intangible (deterioration in health-related quality of life costs of the disease will contribute to an increase in national health service expenditure, which will correspond to 1% of the total health care costs of the nation in the near future. The introduction of biological agents for the treatment of rheumatic diseases has resulted in an increase in the direct costs of RA; however, economic analyses that exclude indirect costs will underestimate the full economic impact of RA. The effectiveness of innovative therapies in preventing disease progression and functional impairment may, over time, attenuate the cost impact of RA in terms of hospitalizations and work absenteeism. Further research is needed to develop estimates of the economic impact of different therapeutic approaches in patients with RA in Italy, in order to provide tools that can drive the choice of the most cost-effective therapeutic option while maintaining high-quality care

  19. Efficacy and Safety Extrapolation Analyses for Atomoxetine in Young Children with Attention-Deficit/Hyperactivity Disorder.

    Science.gov (United States)

    Upadhyaya, Himanshu; Kratochvil, Christopher; Ghuman, Jaswinder; Camporeale, Angelo; Lipsius, Sarah; D'Souza, Deborah; Tanaka, Yoko

    2015-12-01

    This extrapolation analysis qualitatively compared the efficacy and safety profile of atomoxetine from Lilly clinical trial data in 6-7-year-old patients with attention-deficit/hyperactivity disorder (ADHD) with that of published literature in 4-5-year-old patients with ADHD (two open-label [4-5-year-old patients] and one placebo-controlled study [5-year-old patients]). The main efficacy analyses included placebo-controlled Lilly data and the placebo-controlled external study (5-year-old patients) data. The primary efficacy variables used in these studies were the ADHD Rating Scale-IV Parent Version, Investigator Administered (ADHD-RS-IV-Parent:Inv) total score, or the Swanson, Nolan and Pelham (SNAP-IV) scale score. Safety analyses included treatment-emergent adverse events (TEAEs) and vital signs. Descriptive statistics (means, percentages) are presented. Acute atomoxetine treatment improved core ADHD symptoms in both 6-7-year-old patients (n=565) and 5-year-old patients (n=37) (treatment effect: -10.16 and -7.42). In an analysis of placebo-controlled groups, the mean duration of exposure to atomoxetine was ∼ 7 weeks for 6-7-year-old patients and 9 weeks for 5-year-old patients. Decreased appetite was the most common TEAE in atomoxetine-treated patients. The TEAEs observed at a higher rate in 5-year-old versus 6-7-year-old patients were irritability (36.8% vs. 3.6%) and other mood-related events (6.9% each vs. atomoxetine may improve ADHD symptoms, but possibly to a lesser extent than in older children, with some adverse events occurring at a higher rate in 5-year-old patients.

  20. Development, implementation and critique of a bioethics framework for pharmaceutical sponsors of human biomedical research.

    Science.gov (United States)

    Van Campen, Luann E; Therasse, Donald G; Klopfenstein, Mitchell; Levine, Robert J

    2015-11-01

    Pharmaceutical human biomedical research is a multi-dimensional endeavor that requires collaboration among many parties, including those who sponsor, conduct, participate in, or stand to benefit from the research. Human subjects' protections have been promulgated to ensure that the benefits of such research are accomplished with respect for and minimal risk to individual research participants, and with an overall sense of fairness. Although these protections are foundational to clinical research, most ethics guidance primarily highlights the responsibilities of investigators and ethics review boards. Currently, there is no published resource that comprehensively addresses bioethical responsibilities of industry sponsors; including their responsibilities to parties who are not research participants, but are, nevertheless key stakeholders in the endeavor. To fill this void, in 2010 Eli Lilly and Company instituted a Bioethics Framework for Human Biomedical Research. This paper describes how the framework was developed and implemented and provides a critique based on four years of experience. A companion article provides the actual document used by Eli Lilly and Company to guide ethical decisions regarding all phases of human clinical trials. While many of the concepts presented in this framework are not novel, compiling them in a manner that articulates the ethical responsibilities of a sponsor is novel. By utilizing this type of bioethics framework, we have been able to develop bioethics positions on various topics, provide research ethics consultations, and integrate bioethics into the daily operations of our human biomedical research. We hope that by sharing these companion papers we will stimulate discussion within and outside the biopharmaceutical industry for the benefit of the multiple parties involved in pharmaceutical human biomedical research.

  1. Large-eddy simulation of stratified atmospheric flows with the CFD code Code-Saturne

    International Nuclear Information System (INIS)

    Dall'Ozzo, Cedric

    2013-01-01

    Large-eddy simulation (LES) of the physical processes in the atmospheric boundary layer (ABL) remains a complex subject. LES models have difficulties to capture the evolution of the turbulence in different conditions of stratification. Consequently, LES of the whole diurnal cycle of the ABL including convective situations in daytime and stable situations in the nighttime is seldom documented. The simulation of the stable atmospheric boundary layer which is characterized by small eddies and by weak and sporadic turbulence is especially difficult. Therefore The LES ability to well reproduce real meteorological conditions, particularly in stable situations, is studied with the CFD code developed by EDF R and D, Code-Saturne. The first study consist in validate LES on a quasi-steady state convective case with homogeneous terrain. The influence of the sub-grid-scale models (Smagorinsky model, Germano-Lilly model, Wong-Lilly model and Wall-Adapting Local Eddy-viscosity model) and the sensitivity to the parametrization method on the mean fields, flux and variances are discussed. In a second study, the diurnal cycle of the ABL during Wangara experiment is simulated. The deviation from the measurement is weak during the day, so this work is focused on the difficulties met during the night to simulate the stable atmospheric boundary layer. The impact of the different sub-grid-scale models and the sensitivity to the Smagorinsky constant are been analysed. By coupling radiative forcing with LES, the consequences of infra-red and solar radiation on the nocturnal low level jet and on thermal gradient, close to the surface, are exposed. More, enhancement of the domain resolution to the turbulence intensity and the strong atmospheric stability during the Wangara experiment are analysed. Finally, a study of the numerical oscillations inherent to Code-Saturne is realized in order to decrease their effects. (author) [fr

  2. Generation and characterization of tabalumab, a human monoclonal antibody that neutralizes both soluble and membrane-bound B-cell activating factor

    Directory of Open Access Journals (Sweden)

    Manetta J

    2014-08-01

    Full Text Available Joseph Manetta, Holly Bina, Paul Ryan, Niles Fox, Derrick R Witcher, Kristine Kikly Biotechnology Discovery Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA Abstract: B-cell activating factor (BAFF is a B-cell survival factor with a key role in B-cell homeostasis and tolerance. Dysregulated BAFF expression may contribute to autoimmune diseases or B-cell malignancies via effects on abnormal B-lymphocyte activation, proliferation, survival, and immunoglobulin secretion. Monoclonal antibodies were generated against human BAFF, characterized for species specificity and affinity, and screened for the ability to neutralize both membrane-bound and soluble BAFF. In addition, studies were undertaken to determine the relative potency of membrane-bound and soluble BAFF. Tabalumab has a high affinity for human, cynomolgus monkey, and rabbit BAFF. No binding to mouse BAFF was detected. Tabalumab was able to neutralize soluble human, cynomolgus monkey, or rabbit BAFF with equal potency. Our data demonstrate that membrane-bound BAFF can be a more potent stimulus for B-cells than soluble BAFF, and tabalumab also neutralized membrane-bound BAFF. Tabalumab prevented BAFF from binding to BAFF receptors and demonstrated pharmacodynamic effects in human BAFF transgenic mice. Tabalumab is a high-affinity human antibody with neutralizing activity against membrane-bound and soluble BAFF. Given our findings that membrane-bound BAFF can have greater in vitro potency than soluble BAFF, neutralization of both forms of BAFF is likely to be important for optimal therapeutic effect. Keywords: autoimmunity, B-cell malignancies, B-cell survival factor, BAFF

  3. An industry update: the latest developments in therapeutic delivery.

    Science.gov (United States)

    Simpson, Iain

    2018-01-01

    This industry update covers the period from 1 September through 30 September 2017, and is based on information sourced from company press releases, scientific literature, patents and various news websites. The month saw the US FDA approve three new molecular entities, Aliqopa (copanlisib dihydrochloride) (Bayer Healthcare); Solosec (secnidazole) (Symbiomix Therapeutics) and Verzenio (abemaciclib) (Eli Lilly and Co). Intarcia Therapeutics Inc. has its application for approval of a novel drug device combination of exenatide for the treatment of diabetes rejected by FDA but said that it will work to address the concerns and refile the application. The impact of biosimilars in the market is steadily increasing with seven biosimilars approved in the USA and Sandoz hoping to add to this with its announcement that FDA has accepted its Biologics License Application for a biosimilar version of Roche's Rituxan. Circassia announced positive top line results of a respiratory drug, Duaklir (for the treatment of chronic obstructive pulmonary disease) and Sarepta (for its new treatment for Duchenne muscular dystrophy). Axovant Sciences Ltd announced the failure if its drug Intepirdine in the treatment of Alzheimer's, adding to a growing list of drug failures in this area. There were a number of developments in the area of oncology with Bristol-Myers Squibb and Infinity Pharmaceuticals announcing an expansion of their collaboration looking at combination treatments, as well as Eli Lilly and Co's approval for Verzenio. Rani Therapeutics and Intra-Cellular Therapies announced successful funding rounds to support their drug programs. Allergan announced a novel licensing deal for its dry eye drug, Restasis, which it hopes would allow it to stave off patent challenges from several companies looking to develop generic versions of the drug. New research suggests that loss of sense of smell can be linked to an increased risk of developing Parkinson's disease.

  4. Correlation between pain response and improvements in patient-reported outcomes and health-related quality of life in duloxetine-treated patients with diabetic peripheral neuropathic pain

    Directory of Open Access Journals (Sweden)

    Ogawa K

    2015-08-01

    Full Text Available Kei Ogawa,1 Shinji Fujikoshi,2 William Montgomery,3 Levent Alev1 1Medical Science, 2Statistical Science, Eli Lilly Japan K.K., Kobe, Japan; 3Global Patient Outcomes and Real World Evidence, Eli Lilly Australia Pty Ltd, West Ryde, NSW, Australia Objective: We assessed whether quality of life (QoL improvement in duloxetine-treated patients with diabetic peripheral neuropathic pain (DPNP correlates with the extent of pain relief.Methods: Pooled data from three multicountry, double-blind, 12-week, placebo-controlled trials of duloxetine-treated (duloxetine 60 mg once daily; total number =335 patients with DPNP were analyzed. Based on improvement in 24-hour average pain scores, patients were stratified into four groups. Improvement in QoL, which was measured as the change from baseline in two patient-reported health outcome measures (Short Form [SF]-36 and five-dimension version of the EuroQol Questionnaire [EQ-5D], was evaluated and compared among the four groups. Pearson’s correlation coefficient was calculated to assess the correlation between improvement in pain scores and improvement in QoL.Results: The group with more pain improvement generally showed greater mean change from baseline in all of the SF-36 scale scores and on the EQ-5D index. Pearson’s correlation coefficients ranged from 0.114 to 0.401 for the SF-36 scale scores (P<0.05, and it was 0.271 for the EQ-5D (P<0.001.Conclusion: Improvement in pain scores was positively correlated with improvement in QoL and patient-reported outcomes in duloxetine-treated patients. Keywords: diabetic peripheral neuropathic pain, duloxetine, efficacy, function, quality of life

  5. Long-term efficacy of adalimumab in the treatment of uveitis associated with juvenile idiopathic arthritis

    Directory of Open Access Journals (Sweden)

    Kotaniemi K

    2011-10-01

    Full Text Available Kaisu Kotaniemi1,2, Hanna Säilä2, Hannu Kautiainen31Helsinki University Hospital, Helsinki, Finland; 2Orton Orthopaedic Hospital and Rehabilitation Unit, Helsinki, Finland; 3Unit of Primary Health Care, Kuopio University Hospital, Kuopio, FinlandBackground: The purpose of this study was to investigate the long-term effects of adalimumab, a tumor necrosis factor alpha antagonist, in the treatment of uveitis associated with juvenile idiopathic arthritis.Methods: Adalimumab was initiated in 94 patients with juvenile idiopathic arthritis to treat active arthritis and/or active associated uveitis. In 18 patients, therapy was discontinued after a short period because of inefficacy or side effects. The activity of uveitis (using Standardized Uveitis Nomenclature [SUN] criteria and clinical examination and arthritis (number of swollen or active joints was evaluated at the start and at end of the study.Results: At the end of the study, uveitis was under good clinical control in two thirds of 54 patients (31% did not need any local treatment and 35% used only 1–2 corticosteroid drops a day, and one third had active uveitis (at least three corticosteroid drops a day. According to SUN criteria, adalimumab treatment for uveitis showed improved activity (a two-fold decrease in uveitis activity in 28% of patients, with a moderate response in 16 patients, no change in a further 16 patients, and worsening activity (a two-fold increase in uveitis activity in 13% of patients. The overall proportion of patients with active arthritis decreased. At the beginning of the study, 69% of patients with uveitis had more than two active joints, and at the end of the study only 27% had active joint disease. In 27 patients with juvenile idiopathic arthritis without uveitis on adalimumab, the number of active joints decreased from 93% to 59%. Systemic corticosteroid treatment could be stopped in 22% of patients with uveitis and in 11% of those without uveitis. Most of the

  6. The Budget Impact of Including Necitumumab on the Formulary for First-Line Treatment of Metastatic Squamous Non-Small Cell Lung Cancer: U.S. Commercial Payer and Medicare Perspectives.

    Science.gov (United States)

    Bly, Christopher A; Molife, Cliff; Brown, Jacqueline; Tawney, Mahesh K; Carter, Gebra Cuyun; Cinfio, Frank N; Klein, Robert W

    2018-06-01

    ,812 (13.5%), and disease costs increased by $7,951 (0.4%), whereas adverse event costs decreased by $1,368 (0.5%) in year 1. From the Medicare perspective, the overall year 1 incremental budget impact was $438,056 ($0.037 PMPM, $3,112 PPPY), representing a 3.0% cost increase. The higher incremental budget in Medicare, compared with commercial plans, was due to higher msqNSCLC incidence in the older Medicare patients (154 vs. 30 patients, respectively). Results were most sensitive to Neci drug costs. Based on projected market shares, coverage for first-line therapy with Neci + GCis appeared to modestly affect overall U.S. health care budgets for msqNSCLC-related care. Given the small eligible patient population, the PMPM budgetary impact on a commercial health plan of reimbursing Neci + GCis in the first year was less than $0.01, rising with increased use of Neci + GCis to $0.025 in the third year. The real-world effect of Neci + GCis needs to be evaluated to validate this analysis; however, these findings may help policymakers in making coverage decisions for Neci + GCis. This study was funded by Eli Lilly and Company. Molife, Brown, Tawney, and Cuyun Carter are equity holders and employees of Eli Lilly and Company. Bly, Cinfio, and Klein are employees of Medical Decision Modeling, which received funding from Eli Lilly and Company to conduct this research and prepare this manuscript.

  7. Efficacy comparison of duloxetine and SSRIs at doses approved in Japan

    Directory of Open Access Journals (Sweden)

    Harada E

    2015-01-01

    Full Text Available Eiji Harada,1 Alexander Schacht,2 Tsukasa Koyama,3 Lauren Marangell,4,5 Toshinaga Tsuji,6 Rodrigo Escobar41Medical Science, Eli Lilly Japan K.K, Kobe, Japan; 2Global Statistical Sciences, Eli Lilly and Company, Bad Homburg, Germany; 3Clinical Research Center, Ohyachi Hospital, Sapporo, Japan; 4Eli Lilly and Company, Indianapolis, IN, 5The University of Texas Health Science Center, Houston, TX, USA; 6Medical Affairs, Shionogi & Co Ltd, Osaka, JapanBackground: Approved doses of antidepressants in Japan are usually lower than those in the USA and European Union, but to date meta-analyses comparing antidepressants have all used the higher doses approved in the USA and European Union and often have used indirect comparisons. The purpose of this study was to conduct an integrated database analysis of patient level data to compare the effects of duloxetine with those of selective serotonin reuptake inhibitors (SSRIs at the doses approved in Japan.Methods: Pooled data were analyzed from four randomized, double-blind, placebo-controlled studies that compared duloxetine at the dose range approved in Japan (40–60 mg/day with other SSRIs (paroxetine 20 mg/day or escitalopram 10 mg/day and placebo in patients with major depressive disorder. In total, 1,694 patients were included in the analysis (duloxetine, n=688; selective serotonin reuptake inhibitors, n=690; placebo, n=316. The primary outcome measure was the mean change from baseline at week 8 in 17-item Hamilton Rating Scale for Depression (HAMD17 total and subscale scores.Results: Duloxetine and both selective serotonin reuptake inhibitors were superior to placebo in HAMD17 total score at week 8 in both the all-randomized group and the more severe subgroup (HAMD17 total scores ≥19. Duloxetine was superior to SSRIs in improving the HAMD17 Retardation subscale score (least squares mean difference [95% confidence interval]: all-randomized group, −0.33 [−0.60, −0.07], P=0.015; severe subgroup,

  8. Adherence and persistence with branded antidepressants and generic SSRIs among managed care patients with major depressive disorder

    Directory of Open Access Journals (Sweden)

    Xianchen Liu

    2011-03-01

    Full Text Available Xianchen Liu1,2, Yi Chen3, Douglas E Faries31Former employee, Eli Lilly and Company, Indianapolis, Indiana, USA; 2Indiana University Department of Psychiatry, Indianapolis, Indiana, USA; 3Eli Lilly and Company, Indianapolis, Indiana, USAObjective: This study compared adherence and persistence of three branded antidepressants: the serotonin and norepinephrine reuptake inhibitors (SNRIs duloxetine and venlafaxine XR, and the selective serotonin reuptake inhibitor (SSRI escitalopram; and generic selective SSRIs, and examined demographic and clinical predictors of adherence and persistence in patients with major depressive disorder in usual care settings.Method: A total of 44,026 patients (18 to 64 years from a large commercial administrative claims database were classified as initiators of duloxetine (n = 7,567, venlafaxine XR (n = 6,106, escitalopram (n = 10,239, or generic SSRIs (n = 20,114 during 2006. Adherence was defined as the medication possession ratio of ≥ 0.8 and persistence as the length of therapy without exceeding a 15-day gap. Pairwise comparisons from multivariate logistic regression and Cox proportional hazards models were performed to examine predictors of adherence and persistence.Results: Adherence rate after one year was significantly higher in duloxetine recipients (38.1% than patients treated with venlafaxine XR (34.0%, escitalopram (25.4%, or generic SSRIs (25.5% (all P < 0.01. Duloxetine recipients stayed on medication longer (158.5 days than those receiving venlafaxine XR (149.6 days, escitalopram (129.1 days, or generic SSRIs (130.2 days (all P < 0.001. Compared with patients treated with escitalopram or generic SSRIs, venlafaxine XR recipients had better adherence and longer persistence (P < 0.001. In addition, being aged 36 years or more, hypersomnia, anxiety disorders, and prior use of antidepressants were associated with increased adherence and persistence, while the opposite was true for comorbid chronic pain

  9. The relationship between pain severity and patient-reported outcomes among patients with chronic low back pain in Japan

    Directory of Open Access Journals (Sweden)

    Montgomery W

    2016-06-01

    Full Text Available William Montgomery,1 Jeffrey Vietri,2 Jing Shi,3 Kei Ogawa,4 Sawako Kariyasu,4 Levent Alev,4 Masaya Nakamura5 1Eli Lilly Australia Pty Ltd., Sydney, NSW, Australia; 2Health Outcomes Practice, Kantar Health, Horsham, PA, 3Health Outcomes Practice, Kantar Health, Princeton, NJ, USA; 4Eli Lilly Japan K.K., Kobe, Japan; 5Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan Objective: The aim of this study was to quantify the impact of pain severity on patient-reported outcomes among individuals diagnosed with chronic low back pain in Japan. Methods: Data were provided by the 2012 Japan National Health and Wellness Survey (N=29,997, a web-based survey of individuals in Japan aged ≥18 years. This analysis included respondents diagnosed with low back pain of ≥3-month duration. Measures included the revised Medical Outcomes Study 36-Item Short-Form Survey Instrument, the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7 scale, the Work Productivity and Activity Impairment: General Health questionnaire, and self-reported all-cause health care visits (6 months. Generalized linear models were used to assess the relationship between outcomes and severity of pain in the past week as reported on a numeric rating scale ranging from 0 (no pain to 10 (pain as bad as you can imagine, controlling for length of diagnosis, sociodemographics, and general health characteristics. Results: A total of 290 respondents were included in the analysis; mean age was 56 years, 41% were females, and 56% were employed. Pain severity was 3/10 for the first quartile, 5/10 for the median, and 7/10 for the third quartile of this sample. Increasing severity was associated with lower scores for mental and physical component summaries and Short-Form 6D health utility, higher depression (Patient Health Questionnaire-9 and anxiety (Generalized Anxiety Disorder-7 scores, greater absenteeism and presenteeism, greater activity impairment

  10. Incidence and impact of pain conditions and comorbid illnesses

    Directory of Open Access Journals (Sweden)

    Davis JA

    2011-10-01

    Full Text Available Jessica A Davis, Rebecca L Robinson, Trong Kim Le, Jin XieLilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USABackground: Individuals with pain often present with more than one painful condition. The purpose of this study was to characterize the rates of comorbidity, pain medication use, and health care costs for 23 selected pain conditions in a large health plan using administrative claims data from 2005 to 2007.Methods: Eligible patients included 1,211,483 adults with at least one pain condition during the one-year study period. Pain condition cohorts were classified based on the first diagnosis present in the claims during the study period.Results: Musculoskeletal pain conditions were among the most prevalent cohorts including low back pain, osteoarthritis, and fibromyalgia. Cancer pain was the least prevalent cohort. Conditions with the lowest illness severity included migraine and painful bladder syndrome cohorts, while cohorts with diabetic neuropathy, human immunodeficiency virus (HIV-associated pain, and cancer pain were the most severe. Across cohorts, the mean number of comorbid pain conditions ranged from 1.39 (for cancer pain and migraine to 2.65 (for multiple sclerosis pain. High rates of mental health conditions were found in cohorts with HIV-associated pain and multiple sclerosis pain (42.59% and 34.78% and were lowest among cohorts with rheumatoid arthritis and psoriatic arthropathy (12.73% and 13.31%, respectively. Rates of sleep disorders ranged from 5.47% (for painful bladder syndrome to 11.59% (for multiple sclerosis pain. Overall, patients averaged 3.53 unique pain medications during the study period. Considerable annual total health care costs were observed in the cancer pain cohort and the lowest costs were observed in the postherpetic neuropathy, surgically-induced pain, migraine, and irritable bowel syndrome cohorts. Costs attributed to pain were highest among the multiple sclerosis, HIV, and cancer

  11. Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports.

    Science.gov (United States)

    Sharma, Tarang; Guski, Louise Schow; Freund, Nanna; Gøtzsche, Peter C

    2016-01-27

    To study serious harms associated with selective serotonin and serotonin-norepinephrine reuptake inhibitors.Design Systematic review and meta-analysis. Mortality and suicidality. Secondary outcomes were aggressive behaviour and akathisia. Clinical study reports for duloxetine, fluoxetine, paroxetine, sertraline, and venlafaxine obtained from the European and UK drug regulators, and summary trial reports for duloxetine and fluoxetine from Eli Lilly's website. Double blind placebo controlled trials that contained any patient narratives or individual patient listings of harms. Two researchers extracted data independently; the outcomes were meta-analysed by Peto's exact method (fixed effect model). We included 70 trials (64,381 pages of clinical study reports) with 18,526 patients. These trials had limitations in the study design and discrepancies in reporting, which may have led to serious under-reporting of harms. For example, some outcomes appeared only in individual patient listings in appendices, which we had for only 32 trials, and we did not have case report forms for any of the trials. Differences in mortality (all deaths were in adults, odds ratio 1.28, 95% confidence interval 0.40 to 4.06), suicidality (1.21, 0.84 to 1.74), and akathisia (2.04, 0.93 to 4.48) were not significant, whereas patients taking antidepressants displayed more aggressive behaviour (1.93, 1.26 to 2.95). For adults, the odds ratios were 0.81 (0.51 to 1.28) for suicidality, 1.09 (0.55 to 2.14) for aggression, and 2.00 (0.79 to 5.04) for akathisia. The corresponding values for children and adolescents were 2.39 (1.31 to 4.33), 2.79 (1.62 to 4.81), and 2.15 (0.48 to 9.65). In the summary trial reports on Eli Lilly's website, almost all deaths were noted, but all suicidal ideation events were missing, and the information on the remaining outcomes was incomplete. Because of the shortcomings identified and having only partial access to appendices with no access to case report forms, the harms

  12. Predicting early transition from sub-syndromal presentations to major mental disorders.

    Science.gov (United States)

    Cross, Shane P M; Scott, Jan; Hickie, Ian B

    2017-09-01

    Transition from at-risk state to full syndromal mental disorders is underexplored for unipolar and bipolar disorders compared with psychosis. Prospective, trans-diagnostic study of rates and predictors of early transition from sub-threshold to full syndromal mental disorder. One-year outcome of 243 consenting youth aged 15-25 years with a sub-syndromal presentation of a potentially severe mental disorder. Survival analysis and odds ratio (OR) for predictors of transition identified from baseline clinical and demographic ratings. About 17% ( n =36) experienced transition to a major mental disorder. Independent of syndromal diagnosis, transition was significantly more likely in individuals who were NEET (not in education, employment or training), in females and in those with more negative psychological symptoms (e.g. social withdrawal). NEET status and negative symptoms are modifiable predictors of illness trajectory across diagnostic categories and are not specific to transition to psychosis. I.B.H. has been a Commissioner in Australia's National Mental Health Commission since 2012. He was a board member of headspace: National Youth Mental Health Foundation until January 2012. He has led a range of community-based and pharmaceutical industry-supported depression awareness and education and training programmes. He has led projects for health professionals and the community supported by governmental, community agency and pharmaceutical industry partners (Wyeth, Eli Lilly, Servier, Pfizer, AstraZeneca) for the identification and management of depression and anxiety. He has received honoraria for presentations of his own work at educational seminars supported by a number of non-government organisations and the pharmaceutical industry (including Servier, Pfizer, AstraZeneca and Eli Lilly). He is a member of the Medical Advisory Panel for Medibank Private and also a board member of Psychosis Australia Trust. He leads an investigator-initiated study of the effects of

  13. Associations among depression severity, painful physical symptoms, and social and occupational functioning impairment in patients with major depressive disorder: a 3-month, prospective, observational study

    Directory of Open Access Journals (Sweden)

    Harada E

    2017-09-01

    Full Text Available Eiji Harada,1 Yoichi Satoi,2 Atsushi Kuga,1 Hirofumi Tokuoka,1 Toshiaki Kikuchi,3 Koichiro Watanabe,4 Levent Alev,1 Masaru Mimura3 1Biomedicine, Medicines Development Unit Japan, Eli Lilly Japan K.K, Kobe, Japan; 2Statistical Science, Eli Lilly Japan K.K., Kobe, Japan; 3Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; 4Department of Neuropsychiatry, Kyorin University School of Medicine, Tokyo, Japan Purpose: To investigate associations among depression severity, painful physical symptoms (PPS, and social and occupational functioning impairment in patients with major depressive disorder (MDD who had achieved complete remission (CR or partial remission (PR after acute treatment.Patients and methods: This was a 12-week, multicenter, prospective, observational study. Patients with MDD treated with an antidepressant medication for the previous 12 weeks (±3 weeks who had achieved CR (defined as a 17-item Hamilton Rating Scale for Depression [HAM-D17] score ≤7 or PR (HAM-D17 score ≥8 and ≤8 were enrolled. Depression severity, PPS, and impairment in social and occupational functioning were assessed using the HAM-D17, the Brief Pain Inventory (Short Form (BPI-SF, and the Social and Occupational Functioning Assessment Scale (SOFAS, respectively, at enrollment (Week 12 and after 12 weeks (Week 24.Results: Overall, 323 Japanese patients with MDD were enrolled (CR n=158, PR n=165 and 288 patients completed the study (CR n=139, PR n=149. HAM-D17 and SOFAS scores were strongly and negatively correlated at enrollment (Week 12; P<0.0001 and Week 24 (P<0.0001. A weak negative correlation between the BPI-SF and SOFAS was observed at Week 24 (P=0.0011, but not at enrollment (P=0.164. Remission status at enrollment (CR or PR was associated with achieving normal social and occupational functioning (SOFAS score ≥80 at Week 24 in patients who had not achieved normal social and occupational functioning (SOFAS score <80 at

  14. Evaluating preferences for profiles of glucagon-like peptide-1 receptor agonists among injection-naive type 2 diabetes patients in Japan

    Directory of Open Access Journals (Sweden)

    Gelhorn HL

    2016-07-01

    Full Text Available Heather L Gelhorn,1 Elizabeth D Bacci,2 Jiat Ling Poon,1 Kristina S Boye,3 Shuichi Suzuki,4 Steven M Babineaux3 1Outcomes Research, Evidera, Bethesda, MD, 2Evidera, Seattle, WA, 3Global Patient Outcomes and Real World Evidence, Eli Lilly and Company, Indianapolis, IN, USA; 4Medicines Development Unit Japan, Eli Lilly Japan, Kobe, Japan Objective: The objective of this study was to use a discrete choice experiment (DCE to estimate patients’ preferences for the treatment features, safety, and efficacy of two specific glucagon-like peptide-1 receptor agonists, dulaglutide and liraglutide, among patients with type 2 diabetes mellitus (T2DM in Japan.Methods: In Japan, patients with self-reported T2DM and naive to treatment with self-injectable medications were administered a DCE through an in-person interview. The DCE examined the following six attributes of T2DM treatment, each described by two levels: “dosing frequency”, “hemoglobin A1c change”, “weight change”, “type of delivery system”, “frequency of nausea”, and “frequency of hypoglycemia”. Part-worth utilities were estimated using logit models and were used to calculate the relative importance (RI of each attribute. A chi-square test was used to determine the differences in preferences for the dulaglutide versus liraglutide profiles.Results: The final evaluable sample consisted of 182 participants (mean age: 58.9 [standard deviation =10.0] years; 64.3% male; mean body mass index: 26.1 [standard deviation =5.0] kg/m2. The RI values for the attributes in rank order were dosing frequency (44.1%, type of delivery system (26.3%, frequency of nausea (15.1%, frequency of hypoglycemia (7.4%, weight change (6.2%, and hemoglobin A1c change (1.0%. Significantly more participants preferred the dulaglutide profile (94.5% compared to the liraglutide profile (5.5%; P<0.0001.Conclusion: This study elicited the preferences of Japanese T2DM patients for attributes and levels

  15. The economic and humanistic costs of chronic lower back pain in Japan

    Directory of Open Access Journals (Sweden)

    Montgomery W

    2017-06-01

    Full Text Available William Montgomery,1 Masayo Sato,2 Yasuo Nagasaka,2 Jeffrey Vietri3 1Global Patient Outcomes & Real World Evidence, Eli Lilly Australia Pty Ltd., West Ryde, Australia; 2Medical Development Unit Japan, Eli Lilly Japan K.K., Kobe, Japan; 3Kantar Health, Horsham, PA, USA Background: Few data are available that provide estimates of the economic impact of chronic lower back pain (CLBP in Japan. The current study estimated the patient burden and the direct and indirect medical costs associated with CLBP in Japan using data from a large cross-sectional patient survey. CLBP was hypothesized to be associated with a considerable burden of illness and a large economic impact.Methods: Study participants completed the Japan National Health and Wellness Survey in 2014, which included measures of health-related quality of life (HRQoL, work impairment, impairment to daily activities, and healthcare service use. Data from those reporting CLBP (N=392 were contrasted against those from matched controls without back pain, using age and sex-adjusted models.Results: CLBP patients reported significantly lower HRQoL relative to matched controls. Age- and sex-adjusted models estimated mean annual per patient direct and indirect costs attributable to CLBP to be ¥1,820,297 ($15,239 or €12,551 and ¥1,479,899 ($12,389 or €10,203, respectively, with the majority of direct costs related to hospital expenses (¥1,584,759, which is equivalent to $13,267 and €10,927. In estimating the economic impact of CLBP on society, the CLBP respondents were estimated to include 1,508,524 individuals when extrapolated to the Japanese population (815,461 of them employed. Ultimately, this represented approximately ¥1.2 trillion ($10 billion and €8.3 billion per year in lost productivity at the time of this study.Conclusion: This study of patients with CLBP in Japan has shown it to be associated with a significant burden on patients and to have a considerable negative impact on the

  16. Postinjection delirium/sedation syndrome in patients with schizophrenia receiving olanzapine long-acting injection: results from a large observational study.

    Science.gov (United States)

    Meyers, Kristin J; Upadhyaya, Himanshu P; Landry, John L; Chhabra-Khanna, Rashna; Falk, Deborah M; Seetharama Rao, Balasubramanya; Jones, Meghan E

    2017-07-01

    Postinjection delirium/sedation syndrome (PDSS) has been reported uncommonly during treatment with olanzapine long-acting injection (LAI), a sustained-release formulation of olanzapine. The primary aim of the study was to estimate the incidence per injection and per patient of PDSS events in adult patients with schizophrenia who were receiving olanzapine LAI in real-world clinical practice. Secondary aims were to further characterise the clinical presentation of PDSS events, to identify potential risk factors associated with PDSS events and to characterise hospitalisations at baseline and post-baseline. A prospective observational study of adult patients with schizophrenia receiving olanzapine LAI from 24 countries. Data were collected on patient characteristics, olanzapine LAI treatment and any adverse events (AEs). All AEs were reviewed and adjudicated for PDSS using predetermined criteria. There were 46 confirmed PDSS events (0.044% of the 103 505 injections) in 45 patients (1.17% of the 3858 patients). Based on 45 confirmed events with time-to-onset information, 91.1% ( n =41) occurred within 1 h of injection. Time-to-recovery from the event was within 72 h for 95.6% of patients (range 6 h to 11 days). Risk factors for PDSS (per-injection) included high dose (odds ratio (OR) high/low =3.95; P =0.006) and male gender (OR female/male =0.42; P =0.017). Results of this study confirm previously reported PDSS rates, time to onset and recovery, and the severity of PDSS events, and suggest that higher doses and male gender are potential risk factors associated with PDSS. All authors are full-time employees and hold stock/stock options in Eli Lilly, which funded this study. This post-authorisation safety study (PASS) was proposed by Eli Lilly when submitting the original marketing authorisation application for olanzapine LAI in 2007. The protocol and final study report for this European Union regulatory commitment are publicly accessible via the European Network of

  17. Association between pain severity, depression severity, and use of health care services in Japan: results of a nationwide survey

    Directory of Open Access Journals (Sweden)

    Vietri J

    2015-03-01

    Full Text Available Jeffrey Vietri,1 Tempei Otsubo,2 William Montgomery,3 Toshinaga Tsuji,4 Eiji Harada5 1Health Outcomes Practice, Kantar Health, Milan, Italy; 2Tokyo Shinjuku Medical Center, Tokyo, Japan; 3Eli Lilly Australia Pty Ltd., West Ryde, Australia; 4Medical Affairs, Shionogi & Co., Ltd., Osaka, Japan; 5Eli Lilly Japan KK, Kobe, Japan Background: Depression is often associated with painful physical symptoms. Previous research has seldom assessed the relationship between the severity of physical symptoms and the severity of mental and emotional symptoms of depression or other health outcomes, and no such studies have been conducted previously among individuals with depression in Japan. The aim of this study was to assess the relationship between the severity of physical pain and depression and other outcomes among individuals in Japan diagnosed with depression.Methods: Data for individuals aged 18 and older in Japan who reported being diagnosed with depression and also reported physical pain were obtained from the Japan National Health and Wellness Survey. These respondents were characterized on sociodemographics and health characteristics, and the relationship between ratings of severity on pain in the last week and health outcomes were assessed using bivariate correlations and generalized linear models. Measures included the Patient Health Questionnaire for depression severity, Medical Outcomes Study 12-Item Short Form Survey Instrument for health-related quality of life, the Work Productivity and Activity Impairment for work and activity impairment, and 6-month report of health care use.Results: More severe physical pain in the past week was correlated with more severe depression, worse health-related quality of life, lower health utility, greater impairment at work, and more health care provider visits. These relationships remained significant after incorporating sociodemographics and health characteristics in the statistical models

  18. Validation of a patient interview for assessing reasons for antipsychotic discontinuation and continuation

    Directory of Open Access Journals (Sweden)

    Matza LS

    2012-07-01

    Full Text Available Louis S Matza,1 Glenn A Phillips,2 Dennis A Revicki,1 Haya Ascher-Svanum,3 Karen G Malley,4 Andrew C Palsgrove,1 Douglas E Faries,3 Virginia Stauffer,3 Bruce J Kinon,3 A George Awad,5 Richard SE Keefe,6 Dieter Naber71Outcomes Research, United BioSource Corporation, Bethesda, MD, 2Formerly with Eli Lilly and Company, Indianapolis, IN, 3Eli Lilly and Company, Indianapolis, IN, 4Malley Research Programming, Inc, Rockville, MD, USA; 5Department of Psychiatry and Behavioral Sciences; University of Toronto, Toronto, Canada; 6Duke University Medical Center, Durham NC, USA; 7Universitaetsklinikum Hamburg-Eppendorf, Hamburg, GermanyIntroduction: The Reasons for Antipsychotic Discontinuation Interview (RAD-I was developed to assess patients’ perceptions of reasons for discontinuing or continuing an antipsychotic. The current study examined reliability and validity of domain scores representing three factors contributing to these treatment decisions: treatment benefits, adverse events, and distal reasons other than direct effects of the medication.Methods: Data were collected from patients with schizophrenia or schizoaffective disorder and their treating clinicians. For approximately 25% of patients, a second rater completed the RAD-I for assessment of inter-rater reliability.Results: All patients (n = 121; 81 discontinuation, 40 continuation reported at least one reason for discontinuation or continuation (mean = 2.8 reasons for discontinuation; 3.4 for continuation. Inter-rater reliability was supported (kappas = 0.63–1.0. Validity of the discontinuation domain scores was supported by associations with symptom measures (the Positive and Negative Syndrome Scale for Schizophrenia, the Clinical Global Impression – Schizophrenia Scale; r = 0.30 to 0.51; all P < 0.01, patients’ primary reasons for discontinuation, and adverse events. However, the continuation domain scores were not significantly associated with these other indicators

  19. Long-term functional improvements in the 2-year treatment of schizophrenia outpatients with olanzapine long-acting injection

    Directory of Open Access Journals (Sweden)

    Ascher-Svanum H

    2014-06-01

    Full Text Available Haya Ascher-Svanum,1 Diego Novick,2,3 Josep Maria Haro,4 Jordan Bertsch,4 David McDonnell,1 Holland Detke11Eli Lilly and Company, Indianapolis, IN, USA; 2Eli Lilly and Company, Windlesham, Surrey, UK; 3Departament de Psiquiatria, Universitat Autonoma de Barcelona, Spain; 4Parc Sanitari Sant Joan de Déu, Centro de Investigación Biomédica en Red en el Área de Salud Mental, Universitat de Barcelona, Barcelona, SpainBackground: Little is known about the long-term changes in the functioning of schizophrenia patients receiving maintenance therapy with olanzapine long-acting injection (LAI, and whether observed changes differ from those seen with oral olanzapine.Methods: This study describes changes in the levels of functioning among outpatients with schizophrenia treated with olanzapine-LAI compared with oral olanzapine over 2 years. This was a secondary analysis of data from a multicenter, randomized, open-label, 2-year study comparing the long-term treatment effectiveness of monthly olanzapine-LAI (405 mg/4 weeks; n=264 with daily oral olanzapine (10 mg/day; n=260. Levels of functioning were assessed with the Heinrichs–Carpenter Quality of Life Scale. Functional status was also classified as “good”, “moderate”, or “poor”, using a previous data-driven approach. Changes in functional levels were assessed with McNemar’s test and comparisons between olanzapine-LAI and oral olanzapine employed the Student’s t-test. Results: Over the 2-year study, the patients treated with olanzapine-LAI improved their level of functioning (per Quality of Life total score from 64.0–70.8 (P<0.001. Patients on oral ­olanzapine also increased their level of functioning from 62.1–70.1 (P<0.001. At baseline, 19.2% of the olanzapine-LAI-treated patients had a “good” level of functioning, which increased to 27.5% (P<0.05. The figures for oral olanzapine were 14.2% and 24.5%, respectively (P<0.001. Results did not significantly differ between

  20. Benefits of switching from latanoprost to preservative-free tafluprost eye drops: a meta-analysis of two Phase IIIb clinical trials

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    Uusitalo H

    2016-03-01

    Full Text Available Hannu Uusitalo,1 Evgeniy Egorov,2 Kai Kaarniranta,3 Yuri Astakhov,4 Auli Ropo5 On behalf of the Switch Study Tafluprost Study Groups 1Department of Ophthalmology, SILK, University of Tampere, Tampere University Hospital, Tampere, Finland; 2Department of Ophthalmology, The Russian National Research Medical University, Moscow, Russia; 3Department of Ophthalmology, University of Eastern Finland, Kuopio University Hospital, Kuopio, Finland, 4Department of Ophthalmology, First Pavlov State Medical University of St Petersburg, Saint Petersburg, Russia, 5Global Medical Affairs, Santen Oy, Tampere, Finland Introduction: Glaucoma patients frequently exhibit ocular surface side effects during treatment with prostaglandin eye drops. The present work investigated whether glaucoma patients suffering from signs and symptoms of ocular surface disease while using preserved latanoprost eye drops benefited from switching to preservative-free tafluprost eye drops. Patients and methods: The analysis was based on 339 glaucoma patients enrolled in two Phase IIIb trials. The patients were required to have two symptoms, or one sign and one symptom of ocular surface disease at baseline, and at least 6 months preceding treatment with latanoprost eye drops preserved with benzalkonium chloride. All eligible patients were switched from latanoprost to preservative-free tafluprost for a total of 12 weeks. Ocular symptoms and ocular signs were evaluated at baseline and at 2 weeks, 6 weeks, and 12 weeks after commencing treatment with tafluprost. Intraocular pressure (IOP, drop discomfort, and treatment preference were evaluated to investigate the clinical efficacy and patient-related outcomes. Results: After 12 weeks of treatment with preservative-free tafluprost, the incidences of irritation/burning/stinging, foreign body sensation, tearing, itching, and dry eye sensation had diminished to one-third of those reported for preserved latanoprost at baseline. The incidences

  1. Introducing litter quality to the ecosystem model LPJ-GUESS: Effects on short- and long-term soil carbon dynamics

    Science.gov (United States)

    Portner, Hanspeter; Wolf, Annett; Rühr, Nadine; Bugmann, Harald

    2010-05-01

    and 2007 [Rühr(2009)] and present soil carbon stocks [Heim et al.(2009)]. Our Results show, that for short-term soil carbon dynamics, e.g. estimates of heterotrophic soil respiration on an annual basis, the inclusion of the dependency on litter quality is not necessary, as the differences are minor only. However, when considering long-term soil carbon dynamics, e.g. simulated estimates of present soil carbon content, the dependency on litter quality shows effect, as there are correlations with specific site factors such as site location and forest type. The inclusion of the dependence on litter quality therefore may be of importance for the projection of future soil carbon dynamics, as forest types may well be altered due to climatic change. References [Heim et al.(2009)] A. Heim, L. Wehrli, W. Eugster, and M.W.I. Schmidt. Effects of sampling design on the probability to detect soil carbon stock changes at the swiss CarboEurope site Lägeren. Geoderma, 149(3-4):347-354, 2009. [Rühr(2009)] Nadine Katrin Rühr. Soil respiration in a mixed mountain forest : environmental drivers and partitioning of component fluxes. PhD thesis, ETH, 2009. [Smith et al.(2001)] Benjamin Smith, I. Colin Prentice, and Martin T. Sykes. Representation of vegetation dynamics in the modelling of terrestrial ecosystems: comparing two contrasting approaches within european climate space. Global Ecology and Biogeography, 10(6):621-637, 2001. [Tuomi et al.(2008)] Mikko Tuomi, Pekka Vanhala, Kristiina Karhu, Hannu Fritze, and Jari Liski. Heterotrophic soil respiration-Comparison of different models describing its temperature dependence. Ecological Modelling, 211(1-2): 182-190, 2008.

  2. Influence of fluorides upon vegetation. Preliminary tests in gardon uses

    Energy Technology Data Exchange (ETDEWEB)

    Gautier, A; Clausmann, P

    1919-01-01

    Pulverized birchwood charcoal extracted with hot acids and washed in boiling water gave a soil medium containing 1.87 mg F per kg. The soil was composed of purified charcoal, 1000 g; Al/sub 2/O/sub 3/ as a jelly, 120 g; CaCO/sub 3/, 730 g (F = 0.002), humus, 27.3 g; very fertile garden soil, 66.0 (F = 0.007); CaHPO/sub 4/, 24 g; KNO/sub 3/, 34 g; (NH/sub 4/)/sub 2/ SO/sub 4/, 30 g; NaCl, 3.0 g; MgCO/sub 3/, 68 g; MnCl/sub 2/, 0.80 g, ZnCO/sub 3/, 0.07; SiO/sub 2/ as jelly, 17.0; FeSO/sub 4/, 180.0; NaAsO/sub 4/, 1.4 g. This entire mixture contained 11 mg F per kg. Plants were grown in three four-liter pots, A, B, C. The pots contained the above mixture, one with charcoal, another with KF. Pot C contained good garden soil for control. The effects of F were estimated by measuring the height of the plant and when the seed was produced, the weight of the seed. Fluorine exerted a favorable influence upon Gressin alenois, cabbage; Spergula arvensis, Escholtzia California, spinach, yellow day-lilly, viperine, Oignon communis and hemp. An unfavorable influence was observed with dwarf peas and sweet peas.

  3. The Ability of Immunoglobulin Yolk Recognized the Antigen in the Tissue of Ascaridia galli

    Directory of Open Access Journals (Sweden)

    Darmawi

    2012-12-01

    Full Text Available Antigen-antibody reaction is an important tool for the analysis of localization of target molecules, including antigenic protein within worm tissues. The purpose of the present research was to demonstrate the ability of immunoglobulin yolk (IgY anti-excretory/secretory recognized the antigen in the tissue of Ascaridia galli by mean of immunohistochemistry method. The excretory/secretory protein was procured from A. galli and concentrated by mean of vivaspin 30,000 MWCO. IgY was produced by egg yolks of immunized chickens with excretory/secretory, and purified using fast protein liquid chromatography (FPLC method. A. galli adult worms were cut in transversal and longitudinal section of the center and anterior region. Slides were incubated with both primary IgY for overnight at 4 oC and secondary antibody rabbit anti-chicken IgY HRP-conjugate for one hour at room temperature. The slides were stained with 3-amino, 9-ethylcarbazole (AEC chromogen, counterstained with Lillie Mayer Haematoxylin, and mounted in glyserin aqueous mount. Antigen-antibody reaction was investigated under a microscope. The result showed that antigen was appeared in the tissues such as cuticle, epicuticle, buccal cavity, and eggs inside the uterine of A. galli. This research concluded that IgY stimulated by the excretory/secretory was able to recognized the antigen scattered in the tissues of A. galli so the IgY could be applied for immunodiagnostic.

  4. Pharma Success in Product Development—Does Biotechnology Change the Paradigm in Product Development and Attrition.

    Science.gov (United States)

    Evens, Ronald P

    2016-01-01

    The biotechnology segment of the overall biopharma industry has existed for only about 40–45 years, as a driver of new product development. This driving force was initiated with the FDA approval of recombinant human insulin in 1982, originating from the Genentech company. The pharma industry in the early years of 1970s and 1980s engaged with biotechnology companies only to a small extent with their in-licensing of a few recombinant molecules, led by Roche, Eli Lilly, and Johnson and Johnson. However, subsequently and dramatically over the last 25 years, biotechnology has become a primary driver of product and technology innovation and has become a cornerstone in new product development by all biopharma companies. This review demonstrates these evolutionary changes regarding approved products, product pipelines, novelty of the products, FDA approval rates, product sales, financial R&D investments in biotechnology, partnerships, mergers and acquisitions, and patent issues. We now have about 300 biotechnology products approved in USA covering 16 medical disciplines and about 250 indications, with the engagement of 25 pharma companies, along with their biotechnology company innovators and partners. The biotechnology pipeline involves over 1000 molecules in clinical trials, including over 300 molecules associated with the top 10 pharma companies. Product approval rates by the FDA for biotechnology products are over double the rate for drugs. Yes, the R&D paradigm has changed with biotechnology now as one of the major focuses for new product development with novel molecules by the whole biopharma industry.

  5. Open Innovation Drug Discovery (OIDD): a potential path to novel therapeutic chemical space.

    Science.gov (United States)

    Alvim-Gaston, Maria; Grese, Timothy; Mahoui, Abdelaziz; Palkowitz, Alan D; Pineiro-Nunez, Marta; Watson, Ian

    2014-01-01

    The continued development of computational and synthetic methods has enabled the enumeration or preparation of a nearly endless universe of chemical structures. Nevertheless, the ability of this chemical universe to deliver small molecules that can both modulate biological targets and have drug-like physicochemical properties continues to be a topic of interest to the pharmaceutical industry and academic researchers alike. The chemical space described by public, commercial, in-house and virtual compound collections has been interrogated by multiple approaches including biochemical, cellular and virtual screening, diversity analysis, and in-silico profiling. However, current drugs and known chemical probes derived from these efforts are contained within a remarkably small volume of the predicted chemical space. Access to more diverse classes of chemical scaffolds that maintain the properties relevant for drug discovery is certainly needed to meet the increasing demands for pharmaceutical innovation. The Lilly Open Innovation Drug Discovery platform (OIDD) was designed to tackle barriers to innovation through the identification of novel molecules active in relevant disease biology models. In this article we will discuss several computational approaches towards describing novel, biologically active, drug-like chemical space and illustrate how the OIDD program may facilitate access to previously untapped molecules that may aid in the search for innovative pharmaceuticals.

  6. Effect of particle diameter of porous media on flow and heat transfer in a mixing tee

    International Nuclear Information System (INIS)

    Wang, Yongwei; Lu, Tao; Wang, Kuisheng

    2012-01-01

    Highlights: ► Three particle diameter cases of 28 mm, 14 mm and 7 mm were simulated by LES. ► With the diameter decreasing, mixing scale tends to decrease in the mixing tee. ► With the diameter decreasing, thermal mixing is weakened. ► With the diameter decreasing, the thermal stratification is obvious. ► When the particle diameter ratio is 4:2:1, pressure drop ratio is 1:2:4. -- Abstract: Numerical simulations have been carried out to investigate flow and heat transfer in a mixing tee filled with periodic sintered copper spheres. Three particle diameter cases of 28 mm, 14 mm and 7 mm with the array of 4 × 4, 8 × 8 and 16 × 16 at the same porosity of 0.3 have been calculated using large-eddy simulations and the Smagorinsky–Lilly sub-grid scale model. With the particle diameter decreasing, the mixture scale of hot and cold fluid tends to decrease in the mixing tee; the pressure drop of fluid flow through porous media increases. When the particle diameter ratios are 4:2:1 and the specific surface ratios are 1:2:4, the pressure drop ratios are 1:2:4; the thermal mixing in porous media is weakened because the temperature fluctuation decreases and the stratification of hot and cold fluids is observed.

  7. Covariates of depression and high utilizers of healthcare: Impact on resource use and costs.

    Science.gov (United States)

    Robinson, Rebecca L; Grabner, Michael; Palli, Swetha Rao; Faries, Douglas; Stephenson, Judith J

    2016-06-01

    To characterize healthcare costs, resource use, and treatment patterns of survey respondents with a history of depression who are high utilizers (HUds) of healthcare and to identify factors associated with high utilization. Adults with two or more depression diagnoses identified from the HealthCore Integrated Research Database were invited to participate in the CODE study, which links survey data with 12-month retrospective claims data. Patient surveys provided data on demographics, general health, and symptoms and/or comorbidities associated with depression. Similar clinical conditions also were identified from the medical claims. Factors associated with high utilization were identified using logistic regression models. Of 3132 survey respondents, 1921 were included, 193 of whom were HUds (defined as those who incurred the top 10% of total all-cause costs in the preceding 12months). Mean total annual healthcare costs were eightfold greater for HUds than for non-HUds ($US56,145 vs. $US6,954; pcosts/resource use. HUds were prescribed twice as many medications (total mean: 16.86 vs. 8.32; psychotropic mean: 4.11 vs. 2.61; both pcosts in patients with depression. Copyright © 2016 Eli Lilly and Company. Published by Elsevier Inc. All rights reserved.

  8. Comparative assessment of immunization procedures for development of anti proinsulin antisera for radioimmunoassay

    International Nuclear Information System (INIS)

    Nascimento, M. do; Borghi, V.C.; Bellini, M.H.; Mesquita, C.H.; Wajchenberg, B.L.

    1992-08-01

    Two schedules of immunization were employed for developing anti proinsulin antisera for radioimmunoassay. Biosynthetic human proinsulin-h P I (Elli Lilly. US), was injected subcutaneously in guinea pigs in multiple sites. In the first schedule were used 50 u g of h P I and the booster injections were administered 4 weeks after the primary immunization and then at 3-week intervals. In the second schedule was used 250 u g of h P I and boosters were done 7, 9 and 18 weeks later. As the antisera were not sufficiently specific for h P I they were purified and assessed for kinetic of precipitation and avidity. Both immunization schedules gave comparable responses. The antisera generated by the use of 50 u g of h P I presented higher cross-reactivity with insulin while the reactivity with c p eptide was of the same order in both antiserum groups. The avidity was very variable in the two groups and the three most sensitive antisera required 24 h at 4 o C for achieving maximum binding with the 125 I-h P I. However, only one antiserum (from the first group) was suitable for the radioimmunoassay. This study emphasizes the difficulties of making valid comparisons between different immunization procedures, especially in the cases when highest avidity is required. (author)

  9. The Order of the Dolphin: Origins of SETI

    Science.gov (United States)

    Temming, Maria; Crider, Anthony

    2016-01-01

    In 1961, the National Academy of Sciences organized a meeting on the search for extraterrestrial intelligence (SETI) at the National Radio Astronomy Observatory in Green Bank, West Virginia. The ten scientists who attended, including future SETI icons such as Frank Drake and Carl Sagan, represented a variety of scientific fields. At the conclusion of the meeting, the attendees adopted the moniker "The Order of the Dolphin," in honor of participant John Lilly's work on interspecies communication. Since this seminal meeting, researchers in each of the attendees' fields have contributed in some way to the search for intelligent life. This study investigates the circumstances that led to each attendee's invitation to Green Bank and explores SETI as the legacy of this meeting. We will focus in this talk on the SETI connections of two attendees, astronomer Otto Struve and physicist Philip Morrison, both in regards to their personal contributions to SETI and the influence of their work on subsequent SETI research. Specifically, we will examine proposals by Otto Struve for exoplanet discovery methods, and Philip Morrison for radio searches that laid the groundwork for modern SETI.

  10. Low coverage sequencing of three echinoderm genomes: the brittle star Ophionereis fasciata, the sea star Patiriella regularis, and the sea cucumber Australostichopus mollis.

    Science.gov (United States)

    Long, Kyle A; Nossa, Carlos W; Sewell, Mary A; Putnam, Nicholas H; Ryan, Joseph F

    2016-01-01

    There are five major extant groups of Echinodermata: Crinoidea (feather stars and sea lillies), Ophiuroidea (brittle stars and basket stars), Asteroidea (sea stars), Echinoidea (sea urchins, sea biscuits, and sand dollars), and Holothuroidea (sea cucumbers). These animals are known for their pentaradial symmetry as adults, unique water vascular system, mutable collagenous tissues, and endoskeletons of high magnesium calcite. To our knowledge, the only echinoderm species with a genome sequence available to date is Strongylocentrotus pupuratus (Echinoidea). The availability of additional echinoderm genome sequences is crucial for understanding the biology of these animals. Here we present assembled draft genomes of the brittle star Ophionereis fasciata, the sea star Patiriella regularis, and the sea cucumber Australostichopus mollis from Illumina sequence data with coverages of 12.5x, 22.5x, and 21.4x, respectively. These data provide a resource for mining gene superfamilies, identifying non-coding RNAs, confirming gene losses, and designing experimental constructs. They will be important comparative resources for future genomic studies in echinoderms.

  11. Cien años del colorante de Giemsa.

    Directory of Open Access Journals (Sweden)

    José Perea Sasiaín

    2003-03-01

    Full Text Available Esta es una revisión general de los trabajos previos y subsecuentes al hallazgo del colorante de Giemsa, con énfasis en los azules de metileno policromos. Se presenta un breve bosquejo biográfico de Berthold Gustav Carl Giemsa, así como de la constitución y mecanismo de acción de su colorante y el resultado de análisis únicos por HPLC de su azur II (azul de metileno, 63,6%; azur B, 28,6%; azur A 4, 4%; azur C, 1,4%, y tionina, 1,9%. Por tanto, el azur I no era 'puro' sino una mezcla de tionina y todos sus derivados metilados en los grupos amina 3 y 7, muy probablemente preparada por oxidación del azul de metileno en medio ácido como lo definió Lillie. Se tabulan los usos del colorante de Giemsa informados durante los últimos 32 años.

  12. Linear relationships between cherry tomato traits

    Directory of Open Access Journals (Sweden)

    Bruno Giacomini Sari

    Full Text Available ABSTRACT: The objective of this study was to identify the linear relationship between cherry tomato yield components. Two uniformity trials, without treatments, were conducted on Lilli cherry tomato plants in a plastic greenhouse during the 2014 spring/summer season, with the plants in two stems. Variables observed for each plant were mean fruit length, mean fruit width, mean fruit weight, number of bunches, number of fruits per bunch, total number of fruits, and total fruit weight; a Pearson's correlation matrix was used to estimate the relationship between the variables. Path analysis was then performed considering total fruit weight as the main variable and the remaining variables as explanatory. Due to the severe multicollinearity, the variable 'number of fruits per bunch' was eliminated. Pearson's correlation coefficients were significant between explanatory and main variables. Mean fruit weight has a low cause-and-effect relationship with the total weight of fruits produced. A low cause-and-effect relationship was also observed between number of fruits and number of bunches. Cherry tomato productivity is directly related to the number of fruits per plant.

  13. Atomoxetine Increased Effect over Time in Adults with Attention-Deficit/Hyperactivity Disorder Treated for up to 6 Months: Pooled Analysis of Two Double-Blind, Placebo-Controlled, Randomized Trials.

    Science.gov (United States)

    Wietecha, Linda A; Clemow, David B; Buchanan, Andrew S; Young, Joel L; Sarkis, Elias H; Findling, Robert L

    2016-07-01

    Changes in the magnitude of efficacy throughout 26 weeks of atomoxetine treatment, along with impact of dosing, were evaluated in adults with ADHD from two randomized, double-blind, placebo-controlled studies. Pooled placebo (n = 485) and atomoxetine (n = 518) patients, dosed 25, 40, 60, 80 (target dose), or 100 mg daily, were assessed. Change from baseline in Conners' Adult ADHD Rating Scale-Investigator Rated Scale: Screening Version (CAARS) total ADHD symptoms score and Adult ADHD Investigator Symptom Rating Scale (AISRS) total score were analyzed using mixed-model repeated measures, with least squares mean change, effect size, and response rate calculated at 1, 2, 4, 8, 12, 16, 22, and 26 weeks. Decreases on CAARS for atomoxetine- versus placebo-treated patients were consistently statistically significantly greater at every time point beginning at one week (P ≤ 0.006, 0.28 effect size). By 4 weeks, comparison was -13.19 compared with -8.84 (P Atomoxetine response rate (CAARS 50% decrease) continued to increase throughout 26 weeks. Atomoxetine treatment in adults with ADHD was associated with small effect sizes after 4 weeks and moderate effect sizes by 6 months of treatment. The data support increased effect size and response rate over time during longer-term treatment at target dose. © 2016 Eli Lilly and Company. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.

  14. Real-World Dosing Patterns of Atomoxetine in Adults with Attention-Deficit/Hyperactivity Disorder.

    Science.gov (United States)

    Kabul, Samaneh; Alatorre, Carlos; Montejano, Leslie B; Farr, Amanda M; Clemow, David B

    2015-12-01

    The aim was to investigate the dosing patterns of atomoxetine monotherapy in adult patients with attention-deficit/hyperactivity disorder (ADHD) in a retrospective analysis. Adult (≥ 18 years) patients with ADHD newly initiated on atomoxetine with ≥ 1 outpatient pharmacy claim for atomoxetine between January 2006 and December 2011 were selected from the Truven Health MarketScan(®) Commercial database. After a 30-day titration period, dosing patterns of atomoxetine monotherapy were analyzed in the 12 months following initiation. In addition, patient demographic and clinical characteristics were compared to identify characteristics associated with suboptimal versus recommended dosing. Of the 12,412 adult patients with ADHD newly initiated on atomoxetine, 4548 (36.6%) were suboptimally dosed, whereas 3323 (26.7%) were treated at recommended dose. Overall, study patients were treated at a mean (standard deviation [SD]) dose of 68.5 (44.9) mg/day. The suboptimal dosing cohort included significantly more females (54% vs. 44%, P atomoxetine therapy in a real-world setting are often dosed suboptimally. Increasing the awareness on optimal dosing strategy among clinicians and patients is warranted to maximize the therapeutic benefits of atomoxetine among adult patients with ADHD. © 2015 Eli Lilly and Company. CNS Neuroscience and Therapeutics published by John Wiley & Sons Ltd.

  15. Bauhäusler on the Franco-Spanish Border

    Directory of Open Access Journals (Sweden)

    Laura Martínez de Guereñu

    2016-10-01

    Full Text Available This article focuses on the travels of Bauhaus masters and instructors and on the transport of Bauhaus products to Spain in 1929, when the Franco-Spanish border was still culturally permeable. Ludwig Mies van der Rohe and Marcel Breuer introduced their tubular-steel furniture in the Spanish market. Mies and Lilly Reich designed the interiors of all German industrial sections at the Barcelona International Exposition, where the Bauhaus sent objects from its carpentry, metal, and weaving workshops. Josef and Anni Albers traveled to see the exhibition and then went to meet Vassily Kandinsky and Paul Klee, who spent over a month on holiday in the Côte Basque. Albers captured their trip in photo collages, Kandinsky registered his impressions in snapshots, while Klee wrote abundant correspondence and produced drawings. Focusing on the itineraries the Bauhäusler followed, along with the means by which they expressed their travel impressions, this article reveals the effect of travel in their later design attitudes and work. Significant cultural transfers between Germany and Spain took place in a critical moment of European history, suggesting that further developments of these learning experiences might have materialized later on both sides of the border, possibly even reaching across the Atlantic.

  16. Perceptions of Oncologists, Healthcare Policy Makers, Patients and the General Population on the Value of Pharmaceutical Treatments in Oncology.

    Science.gov (United States)

    Sacristán, José A; Lizan, Luís; Comellas, Marta; Garrido, Pilar; Avendaño, Cristina; Cruz-Hernández, Juan J; Espinosa, Javier; Dilla, Tatiana

    2016-11-01

    The purpose of this study was to explore the main factors explaining the relative weight of the different attributes that determine the value of oncologic treatments from the different perspectives of healthcare policy makers (HCPM), oncologists, patients and the general population in Spain. Structured interviews were conducted to assess: (1) the importance of the attributes on treatment choice when comparing a new cancer drug with a standard cancer treatment; (2) the importance of survival, quality of life (QoL), costs and innovation in cancer; and (3) the most worrying side effects related to cancer drugs. A total of 188 individuals participated in the study. For all participants, when choosing treatments, the best rated characteristics were greater efficacy, greater safety, treatment adaptation to patients' individual requirements and the rapid reincorporation of patients to their daily activities. There were important differences among participants in their opinion about survival, QoL and cost. In general, oncologists, patients, and the general population gave greater value to gains in QoL than healthcare policy makers. Compared to other participants healthcare policy makers gave greater importance to the economic impact related to oncology treatments. Gains in QoL, survival, safety, cost and innovation are perceived differently by different groups of stakeholders. It is recommended to consider the perspective of different stakeholders in the assessment of a new cancer drugs to obtain more informed decisions when deciding on the most appropriate treatment to use. Eli Lilly & Co, Madrid (Spain).

  17. Patient perspectives on antipsychotic treatments and their association with clinical outcomes

    Directory of Open Access Journals (Sweden)

    Hong Liu-Seifert

    2010-09-01

    Full Text Available Hong Liu-Seifert1, Olawale O Osuntokun1, Jenna L Godfrey2, Peter D Feldman11Lilly Research Laboratories, Indianapolis, IN, USA; 2Durham Veterans Affairs Medical Center, Durham, NC, USAAbstract: This analysis examined patient-reported attitudes toward antipsychotic medication and the relationship of these attitudes with clinical outcomes and pharmacotherapy adherence. The analysis included three randomized, double-blind studies in patients with schizophrenia, schizoaffective disorder, or schizophreniform disorder diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders 4th Edition and randomly assigned to treatment with olanzapine 5–20 mg/day or another antipsychotic (haloperidol 2–20 mg/day, risperidone 2–10 mg/day, or ziprasidone 80–160 mg/day. Patient-reported improvements were significantly greater for olanzapine (n = 488 versus other treatments (haloperidol n = 145, risperidone n = 158, or ziprasidone n = 271 on multiple Drug Attitude Inventory items. A positive attitude toward medication reported by patients was significantly associated with greater clinical improvement on the Positive and Negative Syndrome Scale and lower discontinuation rates. These results suggest that patients’ perceptions of treatment benefits are associated with objective clinical measures, including reduction of symptom severity and lower discontinuation rates. Furthermore, olanzapine may be associated with more positive treatment attitudes. These findings may contribute to a better understanding of reasons for treatment adherence from patients’ own perspectives.Keywords: antipsychotic agents, medication adherence, patient satisfaction, schizophrenia, treatment efficacy

  18. Hot air impingement on a flat plate using Large Eddy Simulation (LES) technique

    Science.gov (United States)

    Plengsa-ard, C.; Kaewbumrung, M.

    2018-01-01

    Impinging hot gas jets to a flat plate generate very high heat transfer coefficients in the impingement zone. The magnitude of heat transfer prediction near the stagnation point is important and accurate heat flux distribution are needed. This research studies on heat transfer and flow field resulting from a single hot air impinging wall. The simulation is carried out using computational fluid dynamics (CFD) commercial code FLUENT. Large Eddy Simulation (LES) approach with a subgrid-scale Smagorinsky-Lilly model is present. The classical Werner-Wengle wall model is used to compute the predicted results of velocity and temperature near walls. The Smagorinsky constant in the turbulence model is set to 0.1 and is kept constant throughout the investigation. The hot gas jet impingement on the flat plate with a constant surface temperature is chosen to validate the predicted heat flux results with experimental data. The jet Reynolds number is equal to 20,000 and a fixed jet-to-plate spacing of H/D = 2.0. Nusselt number on the impingement surface is calculated. As predicted by the wall model, the instantaneous computed Nusselt number agree fairly well with experimental data. The largest values of calculated Nusselt number are near the stagnation point and decrease monotonically in the wall jet region. Also, the contour plots of instantaneous values of wall heat flux on a flat plate are captured by LES simulation.

  19. Optimization Of Blasting Design Parameters On Open Pit Bench A Case Study Of Nchanga Open Pits

    Directory of Open Access Journals (Sweden)

    Victor Mwango Bowa

    2015-08-01

    Full Text Available Abstract In hard rock mining blasting is the most productive excavation technique applied to fragment insitu rock to the required size for efficient loading and crushing. In order to blast the insitu rock to the desired fragment size blast design parameter such as bench height hole diameter spacing burden hole length bottom charge specific charge and rock factor are considered. The research was carried out as a practical method on Nchanga Open Pits NOP ore Bench to optimize the blasting design parameters that can yield the required fragmentation size thereby reducing the shovel loading times and maximizing efficiency of the subsequent mining unit operations such as hauling and crushing. Fragmentation characteristics such as the mean fragment size were measured by means of a digital measuring tape and predicated using the Kuznetsov equation and rock factor value of ore bench was calculated using Lilly 1986 equations by means of rock characteristics. Traditional blasting design parameters were acquired for NOP and modified using Langerfors and Sharma P.A approaches. Several blast operations were conducted using both traditional and modified blasting design parameters on the same ore bench with the same geological conditions. Loading times of the shovel and fragment sizes were obtained after the blasts from ore bench where both the traditional and modified blasting design parameters were applied. Results show that mean fragment size and loading times were reduced from 51cm and 12minutes to 22cm and 3minutes where traditional and modified blasting design parameters were applied respectively.

  20. International investment agreements and public health: neutralizing a threat through treaty drafting.

    Science.gov (United States)

    Mercurio, Bryan

    2014-07-01

    The high profile investment claims filed by Philip Morris challenging Uruguayan and Australian measures that restrict advertising and logos on tobacco packaging awakened the public health community to the existence and potential detrimental impact of international investment agreements (IIAs). More recently, Eli Lilly challenged Canada's invalidation of a pharmaceutical patent under an IIA. All of the cases claim that the intellectual property rights of the investor were infringed. As a result of these cases, many commentators and activists view IIAs as a threat to public health and have lobbied against their inclusion in ongoing trade negotiations. This article does not argue against IIAs. Instead, it seeks to demonstrate how more sophisticated treaty drafting can neutralize the threat to public health. In this regard, the article seeks to engage members of the public health community as campaigners not against IIAs but as advocates of better treaty drafting to ensure that IIAs do not infringe upon the right of a nation to take non-discriminatory measures for the promotion and protection of the health of their populations.

  1. Nonclinical pharmacology and toxicology of the first biosimilar insulin glargine drug product (BASAGLAR®/ABASAGLAR®) approved in the European Union.

    Science.gov (United States)

    Byrd, Richard A; Owens, Rebecca A; Blackbourne, Jamie L; Coutant, David E; Farmen, Mark W; Michael, M Dodson; Moyers, Julie S; Schultze, A Eric; Sievert, Michael K; Tripathi, Niraj K; Vahle, John L

    2017-08-01

    Basaglar ® /Abasaglar ® (Lilly insulin glargine [LY IGlar]) is a long-acting human insulin analogue drug product granted marketing authorisation as a biosimilar to Lantus ® (Sanofi insulin glargine [SA IGlar]) by the European Medicines Agency. We assessed the similarity of LY IGlar to the reference drug product, European Union-sourced SA IGlar (EU-SA IGlar), using nonclinical in vitro and in vivo studies. No biologically relevant differences were observed for receptor binding affinity at either the insulin or insulin-like growth factor-1 (IGF-1) receptors, or in assays of functional or de novo lipogenic activity. The mitogenic potential of LY IGlar and EU-SA IGlar was similar when tested in both insulin- and IGF-1 receptor dominant cell systems. Repeated subcutaneous daily dosing of rats for 4 weeks with 0, 0.3, 1.0, or 2.0 mg/kg LY IGlar and EU-SA IGlar produced mortalities and clinical signs consistent with severe hypoglycaemia. Glucodynamic profiles of LY IGlar and EU-SA IGlar in satellite animals showed comparable dose-related hypoglycaemia. Severe hypoglycaemia was associated with axonal degeneration of the sciatic nerve; the incidence and severity were low and did not differ between LY IGlar and EU-SA IGlar. These results demonstrated no biologically relevant differences in toxicity between LY IGlar and EU-SA IGlar. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Proton milliprobe analyses of the Gutenberg Bible

    Science.gov (United States)

    Kusko, Bruce H.; Cahill, Thomas A.; Eldred, Robert A.; Schwab, Richard N.

    1984-04-01

    The advent of printing with movable type is properly regarded as the most important technological event in modern cultural history, yet its earliest history is shrouded in mystery. The Davis proton milliprobe has enabled scientists and humanist scholars to collaborate in unlocking the secrets of earliest print, focusing on the contribution of Johannes Gutenberg. The 42-line Gutenberg Bible is not only the first book printed by movable type, it is considered by many to be the finest book every printed. Unfortunately very little is known about the materials and techniques used in this first large scale printing operation. In October 1982 we had the unprecedented opportunity to examine page-by-page the inks, papers, illuminations and binding of volume I of the Doheny Gutenberg Bible. A similar study of the Lilly New Testament (most of volume II) was undertaken in March 1983. The results, some wholly unexpected and very exciting, add a large new body of information about this great work, and give us new enlightenment on the day-to-day production of this first and most important printed book. Moreover, the discovery of the uniqueness of the ink in Gutenberg's Bible, combined with our ability to taken minutely detailed and non-destructive elemental "fingerprints" with the milliprobe beam of all man-made papers and inks, gives us a weapon that has never been available before to investigate some of the controversial basic questions in the history of the origins of printing technology.

  3. Glucagon-Like Peptide-1 Receptor Agonist Use and Renal Impairment: A Retrospective Analysis of an Electronic Health Records Database in the U.S. Population.

    Science.gov (United States)

    Boye, Kristina S; Botros, Fady T; Haupt, Axel; Woodward, Brad; Lage, Maureen J

    2018-04-01

    The study characterizes the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) with and without renal impairment and examines the effects of such use on the clinical outcomes of estimated glomerular filtration rate (eGFR) and glycated hemoglobin (A1c). Data from the Practice Fusion electronic health records database from 1 January 2012 through 30 April 2015 were used. Adults with T2D who received serum creatinine laboratory tests and initiated therapy with a GLP-1 RA (N = 3225) or other glucose-lowering agent (GLA) (N = 37,074) were included in the analysis. The GLP-1 RA cohort was matched to cohorts initiating therapy any other GLA, and multivariable analyses examined the association between GLP-1 RA use and changes in eGFR or A1c at 1 year after therapy initiation. In this study, only 5.7% of patients with an eGFR of Eli Lilly and Company.

  4. A 125I-radiolabelled probe for vinblastine and vindesine radioimmunoassays: applications to measurements of vindesine plasma levels in man after intravenous injections and long-term infusions

    International Nuclear Information System (INIS)

    Rahmani, R.; Barbet, J.; Cano, J.-P.

    1983-01-01

    The transformation of vinblastine into a reactive acid azide was used for the preparation of a vindesine-glycyl-tyrosine conjugate. This conjugate was radiolabelled [ 125 I] and used as a tracer for the radioimmunoassay of vinblastine and vindesine with antisera developed by the Eli Lilly Research Laboratories and by the authors. Its higher specific activity as compared to tritiated vinblastine significantly increases the sensitivity of the assay (0.05 μg/l as compared to 0.6 μg/l). It was then possible to monitor vindesine plasma levels for more than 60 h after intravenous bolus injection and to evaluate the elimination rates more accurately. When plasma levels were also measurable using tritiated vinblastine a satisfactory agreement was observed with determinations performed with radioiodinated vindesine-glycyl-tyrosine. Furthermore, the use of a #betta#-emitting probe simplifies the radioimmunoassay procedure and accordingly increases its reproducibility. A few examples of vindesine level measurements in human plasma collected after bolus intravenous injection and during long-term infusion are given. (Auth.)

  5. Optimizing weight control in diabetes: antidiabetic drug selection

    Directory of Open Access Journals (Sweden)

    S Kalra

    2010-08-01

    Full Text Available S Kalra1, B Kalra1, AG Unnikrishnan2, N Agrawal3, S Kumar41Bharti Hospital, Karnal; 2Amrita Institute of Medical Science, Kochi; 3Medical College, Gwalior; 4Excel Life Sciences, Noida, IndiaDate of preparation: 18th August 2010Conflict of interest: SK has received speaker fees from Novo Nordisk, sanofi-aventis, MSD, Eli Lilly, BMS, and AstraZeneca.Clinical question: Which antidiabetic drugs provide optimal weight control in patients with type 2 diabetes?Results: Metformin reduces weight gain, and may cause weight loss, when given alone or in combination with other drugs. Pioglitazone and rosiglitazone use is associated with weight gain. Use of the glucagon-like peptide-1 (GLP-1 analogs, liraglutide and exenatide, is associated with weight loss. Dipeptidyl peptidase-4 (DPP-4 inhibitors are considered weight-neutral. Results with insulin therapy are conflicting. Insulin detemir provides weight control along with glycemic control.Implementation: • Weight gain is considered an inevitable part of good glycemic control using conventional modalities of treatment such as sulfonylureas.• Use of metformin, weight-sparing insulin analogs such as insulin detemir, and liraglutide, should be encouraged as monotherapy, or in combination with other drugs.Keywords: weight control, diabetes

  6. Design of ultra-stable insulin analogues for the developing world

    Directory of Open Access Journals (Sweden)

    Michael A Weiss

    2013-01-01

    Full Text Available The engineering of insulin analogues illustrates the application of structure-based protein design to clinical medicine. Such design has traditionally been based on structures of wild-type insulin hexamers in an effort to optimize the pharmacokinetic (PK and pharmacodynamic properties of the hormone. Rapid-acting insulin analogues (in chronological order of their clinical introduction, Humalog ® [Eli Lilly & Co.], Novolog ® [Novo-Nordisk], and Apidra ® [Sanofi-Aventis] exploit the targeted destabilization of subunit interfaces to facilitate capillary absorption. Conversely, long-acting insulin analogues exploit the stability of the insulin hexamer and its higher-order self-assembly within the subcutaneous depot to enhance basal glycemic control. Current products either operate through isoelectric precipitation (insulin glargine, the active component of Lantus ® ; Sanofi-Aventis or employ an albumin-binding acyl tether (insulin detemir, the active component of Levemir ® ; Novo-Nordisk. Such molecular engineering has often encountered a trade-off between PK goals and product stability. Given the global dimensions of the diabetes pandemic and complexity of an associated cold chain of insulin distribution, we envisage that concurrent engineering of ultra-stable protein analogue formulations would benefit the developing world, especially for patients exposed to high temperatures with inconsistent access to refrigeration. We review the principal mechanisms of insulin degradation above room temperature and novel molecular approaches toward the design of ultra-stable rapid-acting and basal formulations.

  7. A psychometric evaluation of the Diabetes Symptom Checklist-Revised (DSC-R cognitive distress, fatigue, hyperglycemia, and hypoglycemia subscales in patients with type 1 and type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Naegeli AN

    2010-03-01

    Full Text Available April N Naegeli1, Timothy E Stump2, Risa P Hayes11Global Health Outcomes, Eli Lilly and Company, Indianapolis, IN, USA; 2Consultant, Indianapolis, IN, USAObjective: To explore the use of Diabetes Symptom Checklist-Revised (DSC-R Cognitive Distress, Fatigue, Hyperglycemia, and Hypoglycemia subscales as measures of acute diabetesassociated symptoms in patients with both type 1 and 2 diabetes.Research design and methods: Our study was conducted in context of two international, multicenter, randomized clinical trials for inhaled insulin. Confirmatory factor analyses and assessments of reliability and construct validity were performed.Results: Study participants were 371 patients with type 2 (56% male; mean age, 57 years and 481 with type 1 diabetes (57% male, mean age, 40 years. In both populations a four-factor model was the best fit. Cronbach’s α ≥ 0.79 and intraclass correlation coefficient ≥0.63; subscales correlated (P ≤ 0.05 with measures of well-being and satisfaction (0.12 ≤ r ≤ 0.71. In patients with type 1 diabetes, three subscales correlated (P < 0.05 with A1C.Conclusions: The psychometric properties of the DSC-R Cognitive Distress, Fatigue, Hyperglycemia, and Hypoglycemia suggest they may be utilized in clinical trials as reliable and valid measures of acute symptoms of diabetes.Keywords: Diabetes Symptom Checklist-Revised, DSC-R, type 1 diabetes, type 2 diabetes, psychometric validation

  8. Detection of Chlamydophila psittaci from feral pigeons in environmental samples: problems with currently available techniques.

    Science.gov (United States)

    Geigenfeind, Ila; Haag-Wackernagel, Daniel

    2010-03-01

    Chlamydophila psittaci (Lillie, 1930) Everett et al., 1999, the pathogenic agent of human ornithosis, is widespread in feral pigeon populations and many cases of transmission from feral pigeons to humans have been reported. The aim of the present study was to detect C. psittaci in environmental samples to find out more about possible transmission routes and, therefore, to assess the zoonotic risk for humans. Fecal samples were collected from nest boxes in a feral pigeon loft. Additionally, samples were taken from the feather dust film covering the water surface of public fountains where pigeons regularly bathe. The samples were tested for the presence of chlamydial antigen using an antigen enzyme-linked immunosorbent assay to prove shedding of C. psittaci by feral pigeons. This test detects a genus specific lipopolysaccharide in the outer membrane of the chlamydial bacteria. Samples were tested using the IDEIA PCE Chlamydia Test kit (DakoCytomation) and positive results were verified with IDEIA Chlamydia Blocking Reagents (DakoCytomation). The IDEIA PCE Chlamydia Test yields a high proportion of positive results. However, when IDEIA Chlamydia Blocking was performed, most of the positive results turned out to be negative or could not be interpreted. We conclude that antigen-enzyme-linked immunosorbent assay tests are not suitable for detecting C. psittaci in environmental samples. Previous publications where no blocking test was used should be reconsidered critically. © 2010 ISZS, Blackwell Publishing and IOZ/CAS.

  9. Proosa 1977. Kirjanduse argipäev / Mall Jõgi

    Index Scriptorium Estoniae

    Jõgi, Mall, 1947-

    2008-01-01

    Sisaldab joonealuseid märkusi ja bibliograafiat. - Varem ilmunud Looming 1978, nr. 2. - Ülevaade 1977. aastal ilmunud eesti proosast. Käsitletakse järgmisi autoreid ja nende teoseid: Ustav Mikelsaar "Ohver", Lembit Kivisaar "Vana diivan", Albert Uustulnd "Avali väraval", Asta Põldmäe "Me", Lilli Promet "Tüdrukud taevast", Nikolai Baturin "Leiud kajast", Aadu Hint "Oma saar", Paul Kuusberg "Linnukesega", Aimée Beekman "Sugupuu", Mari Saat "Mida teha emaga?", Veera Saar "Isa niinepuu", Villem Gross "Vaikimise motiivid", Jüri Tuulik "Meretagune asi", Aira Kaal "Teedla Riia aknas põleb tuli", Tõnis Lehtmets "Tume laas", Väino Ilus "Kinsli peremehed", Einar Maasik "Hispaania tants", Aino Müür "Linnuvere lugu", Jaan Kross "Kolme katku vahel" 3. osa, Endel Nirk "Kaanekukk", Paul Kuusberg "Võõras või õige mees", Toomas Vint "Perekondlikud mängud", Ine Viiding "Kümme käsku kaaskodanikele", Mats Traat "Irdinimene. Türgi oad", Teet Kallas "Õhtuvalgus", Teet Kallas "Insener Paberiti juhtum", Einar Maasik "Üksinda detsembris", Enn Vetemaa "Hõbedaketrajad", Herta Laipaik "Kummitus muusikatoas. Doktor Vallaku mõistatus", Raimond Kaugver "Külalisteraamat"

  10. Short outlines of books by Estonian authors / Janika Kronberg, Rutt Hinrikus

    Index Scriptorium Estoniae

    Kronberg, Janika, 1963-

    2003-01-01

    Sinijärv, Karl- Martin. Artutart & 39. Tallinn : Tuum, 2002 ; Beier, Priidu. Monaco. Tartu : P. Beier, 2002 ; Malin, Jaan. Sulle. Tartu : J. Malin, 2003 ; Liiv, Toomas. Luuletused 1968-2002. Tallinn : Tuum, 2003 ; Mägi, Arvo. Katk ja koolera. Tartu : Ilmamaa ; Kross, Jaan. Omaeluloolisus ja alltekst. Tallinn : Eesti Keele Sihtasutus, 2003 ; Kaplinski, Jaan ; Salminen, Johannes. Ööd valged ja mustad. Tallinn : Loomingu Raamatukogu, 2003 ; Kauksi Ülle. Käänüpäiv. Tartu : Kauksi Ülle Mänedsment', 2003 ; Luik, Tõnu. Filosoofiast kõnelda. Tartu : Ilmamaa, 2002 ; Teder, Tarmo. Pööningujutud. Tallinn : Eesti Keele Sihtasutus, 2002 ; Vetemaa, Enn. Minu väga magus elu ehk martsipanimeister. Tallinn : Tänapäev, 2002 ; Põldroos, Enn. Joonik kivi. Tallinn : Eesti Keele Sihtasutus, 2003 ; Suburg, Lilli. Kogutud kirjatööd. Tallinn : Eesti Raamat, 2002 ; Mikelsaar, Henn. Müüritud. Tartu : Ilmamaa, 2003 ; Kaus, Jan. Õndsate tund. Tallinn : Tuum, c2003

  11. The effect of federal and state off-label marketing investigations on drug prescribing: The case of olanzapine.

    Science.gov (United States)

    Wang, Bo; Studdert, David M; Sarpatwari, Ameet; Franklin, Jessica M; Landon, Joan; Kesselheim, Aaron S

    2017-01-01

    In the past decade, the federal government has frequently investigated and prosecuted pharmaceutical manufacturers for illegal promotion of drugs for indications not approved by the Food and Drug Administration (FDA) ("off-label" uses). State governments can choose to coordinate with the federal investigation, or pursue their own independent state investigations. One of the largest-ever off-label prosecutions relates to the atypical antipsychotic drug olanzapine (Zyprexa). In a series of settlements between 2008 and 2010, Eli Lilly paid $1.4 billion to the federal government and over $290 million to state governments. We examined the effect of these settlements on off-label prescribing of this medication, taking advantage of geographical differences in states' involvement in the investigations and the timing of the settlements. However, we did not find a reduction in off-label prescribing; rather, there were no prescribing changes among states that joined the federal investigation, those that pursued independent state investigations, and states that pursued no investigations at all. Since the settlements of state investigations of off-label prescribing do not appear to significantly impact prescribing rates, policymakers should consider alternate ways of reducing the prevalence of non-evidence-based off-label use to complement their ongoing investigations.

  12. Novel Phenotypic Outcomes Identified for a Public Collection of Approved Drugs from a Publicly Accessible Panel of Assays.

    Directory of Open Access Journals (Sweden)

    Jonathan A Lee

    Full Text Available Phenotypic assays have a proven track record for generating leads that become first-in-class therapies. Whole cell assays that inform on a phenotype or mechanism also possess great potential in drug repositioning studies by illuminating new activities for the existing pharmacopeia. The National Center for Advancing Translational Sciences (NCATS pharmaceutical collection (NPC is the largest reported collection of approved small molecule therapeutics that is available for screening in a high-throughput setting. Via a wide-ranging collaborative effort, this library was analyzed in the Open Innovation Drug Discovery (OIDD phenotypic assay modules publicly offered by Lilly. The results of these tests are publically available online at www.ncats.nih.gov/expertise/preclinical/pd2 and via the PubChem Database (https://pubchem.ncbi.nlm.nih.gov/ (AID 1117321. Phenotypic outcomes for numerous drugs were confirmed, including sulfonylureas as insulin secretagogues and the anti-angiogenesis actions of multikinase inhibitors sorafenib, axitinib and pazopanib. Several novel outcomes were also noted including the Wnt potentiating activities of rotenone and the antifolate class of drugs, and the anti-angiogenic activity of cetaben.

  13. Common plant toxicology: A comparison of national and Southwest Ohio data trends on plant poisonings in the 21st century

    International Nuclear Information System (INIS)

    Petersen, Dan D.

    2011-01-01

    Data from the American Association of Poison Control Centers (AAPCC) and the Cincinnati-based Drug and Poison Information Center (DPIC) were analyzed to determine the incidence and trends of human plant poisonings since the year 2000. Approximately 3.4% of the approximately 4.3 million annual calls to the AAPCC centers involved plants, with a higher fraction (4.5%) for pediatric exposures. Nearly 70% of plant exposures occurred in children under six. Only 8% of cases required treatment in a health-care facility, and only 0.1% (in 2008) were considered severe outcomes. The most prominent groups of plants involved in exposures are those containing oxalates, and the most common symptom is gastroenteritis. The top 12 identified plants (in descending order) nationally were Spathiphyllum species (peace lilly), Philodendron species (philodendron), Euphorbia pulcherrima (poinssettia), Ilex species (holly), Phytolacca americana (pokeweed), Toxicodendron radicans (poison ivy), Capsicum (pepper), Ficus (rubber tree, weeping fig), Crassula argentea (jade plant), Diffenbachia (dumb cane), Epipremnum areum (pothos) and Schlumbergera bridesii (Christmas cactus). Broad overlaps between the DPIC and the AAPCC incidence data were noted, with essentially the same plant species in each dataset. The nature of the various toxins, the symptomatology and potential treatments are discussed for the highest ranking plant species.

  14. Current perspectives on chief residents in psychiatry.

    Science.gov (United States)

    Warner, Christopher H; Rachal, James; Breitbach, Jill; Higgins, Michael; Warner, Carolynn; Bobo, William

    2007-01-01

    The authors examine qualitative data from outgoing chief residents in psychiatry from the 2004-2005 academic year to 1) determine common characteristics between programs, 2) examine the residents' perspectives on their experiences, and 3) determine their common leadership qualities. The authors sent out self-report surveys via e-mail to 89 outgoing chief residents who attended the APA/Lilly Chief Resident Executive Leadership Program. Fifty-three (60%) chief residents responded. Although most chief residents are senior residents, over 20% are in their third postgraduate year. Two-thirds of programs have more than one chief resident each year. Most chief residents believe that their "participating" leadership style, existing leadership skills, and interpersonal skills contributed to their overall positive experiences. Successfully performing duties as a chief resident entails functioning in a variety of roles and demands attention to leadership qualities of the individual. Developing existing leadership skills, clarifying expectations, and providing mentorship to chief residents will ensure successful transition into practice, and the advancement of the field of psychiatry.

  15. Indiana Wesleyan University SPS Physics Outreach to Rural Middle School and High School Students

    Science.gov (United States)

    Ostrander, Joshua; Rose, Heath; Burchell, Robert; Ramos, Roberto

    2013-03-01

    The Society of Physics Students chapter at Indiana Wesleyan University is unusual in that it has no physics major, only physics minors. Yet while just over a year old, IWU-SPS has been active in performing physics outreach to middle school and high school students, and the rural community of Grant County. Our year-old SPS chapter consists of majors from Chemistry, Nursing, Biology, Exercise Science, Computer Science, Psychology, Pastoral Studies, and Science Education, who share a common interest in physics and service to the community. IWU currently has a physics minor and is currently working to build a physics major program. Despite the intrinsic challenges, our multi-disciplinary group has been successful at using physics demonstration equipment and hands-on activities and their universal appeal to raise the interest in physics in Grant County. We report our experience, challenges, and successes with physics outreach. We describe in detail our two-pronged approach: raising the level of physics appreciation among the IWU student community and among pre-college students in a rural community of Indiana. Acknowledgements: We acknowledge the support of the Society of Physics Students through a Marsh White Outreach Award and a Blake Lilly Prize.

  16. Using measures to guide the continuous improvement journey: a partnership between quality assurance and toxicology.

    Science.gov (United States)

    Gentry, P E; Sites, D L

    1994-03-01

    It has been said that you cannot improve what you cannot measure. At Eli Lilly and Company, measurement is one of the five pillars of Total Quality. Quality Assurance and Toxicology have partnered in the use of measures to drive improvements in both areas. Quality Assurance and Toxicology have embarked on a journey in Total Quality to achieve customer satisfaction and drive continuous improvement. Measurement in the research and development world has traditionally not been well received. Contrary to popular belief, we have found that many processes can be measured in the research and development environment. Measurement is critical to the continuous improvement of processes because improvements are made using data. In Quality Assurance and Toxicology, the initial measures were put in place to gather baseline data. As we learned from our measures, we customized them to align with all of our processes. This article describes the journey of measuring Quality Assurance and Toxicology, including highlights of implementation strategies and lessons learned along the way.

  17. Patterns of Adherence to Oral Atypical Antipsychotics Among Patients Diagnosed with Schizophrenia.

    Science.gov (United States)

    MacEwan, Joanna P; Forma, Felicia M; Shafrin, Jason; Hatch, Ainslie; Lakdawalla, Darius N; Lindenmayer, Jean-Pierre

    2016-11-01

    abuse (OR = 1.46; 95% CI = 1.26-1.66; P aged 35-54 years (OR = 0.66; 95% CI = 0.46-0.85; P different groups may warrant different types of clinical interventions to prevent hospitalizations, longer hospital stays, and increased clinical complexity. For example, clinicians may consider regular home visits, assertive community treatment, and other related interventions for patients at high risk of immediate discontinuation. Health plans should consider supplementing claims-based adherence measures with new technologies that are able to track patient adherence patterns over time. Otsuka Pharmaceutical Development & Commercialization provided support for this research. MacEwan and Shafrin are employees of Precision Health Economics, which was contracted by Otsuka Pharmaceutical Development & Commercialization to conduct this study. Lakdawalla is the Chief Scientific Officer and a founding partner of Precision Health Economics. Forma is an employee of Otsuka Pharmaceutical Development & Commercialization. Hatch is a former employee of Otsuka Pharmaceutical Development & Commercialization and is a current employee of ODH, Inc. Lindenmayer has received grant/research support from Janssen, Lilly, AstraZeneca, Johnson & Johnson, Pfizer, BMS, Otsuka, Dainippon, and Roche and is a consultant for Janssen, Lilly, Merck, Shire, and Lundbeck. Portions of this study were presented as a poster at the American Society of Clinical Psychopharmacology Annual Meeting in Miami Beach, Florida; June 23, 2015; and at the 28th Annual U.S. Psychiatric and Mental Health Congress; San Diego, California; September 12, 2015. Study concept and design were contributed by Forma, Ladkawalla, MacEwan, and Shafrin, along with Hatch and Lindenmayer. MacEwan, Shafrin, Forma, and Lakdawalla collected the data, along with Hatch and Lindenmayer. Data interpretation was performed by Hatch, Lindenmayer, MacEwan, and Shafrin, assisted by Forma and Lakdawalla. The manuscript was written and revised by MacEwan, Forma

  18. Interventions to treat premature ejaculation: a systematic review short report.

    Science.gov (United States)

    Cooper, Katy; Martyn-St James, Marrissa; Kaltenthaler, Eva; Dickinson, Kath; Cantrell, Anna

    2015-03-01

    Zeneca), topical eutectic mixture for PE (Plethora Solutions Ltd) spray; selective serotonin reuptake inhibitors (SSRIs) - citalopram (Cipramil(®), Lundbeck), escitalopram (Cipralex(®), Lundbeck), fluoxetine, paroxetine, sertraline, dapoxetine (Priligy(®), Menarini), 30 mg or 60 mg; serotonin-noradrenaline reuptake inhibitors - duloxetine (Cymbalta(®), Eli Lilly & Co Ltd); tricyclic antidepressants - inhaled clomipramine 4 mg; phosphodiesterase-5 (PDE5) inhibitors - vardenafil (Levitra(®), Bayer), tadalafil (Cialis(®), Eli Lilly & Co Ltd); opioid analgesics - tramadol (Zydol SR(®), Grünenthal). Improvements in sexual satisfaction and other outcomes compared with placebo were evident for SSRIs, PDE5 inhibitors and tramadol. Outcomes for interventions not compared with placebo were as follows: behavioural therapies - improvements over wait list control in IELT and other outcomes, behavioural therapy plus pharmacotherapy better than either therapy alone; alpha blockers - terazosin (Hytrin(®), AMCO) not significantly different to antidepressants in ejaculation control; acupuncture - improvements over sham acupuncture in IELT, conflicting results for comparisons with SSRIs; Chinese medicine - improvements over treatment as usual; delay device - improvements in IELT when added to stop-start technique; yoga - improved IELT over baseline, fluoxetine better than yoga. Treatment-related AEs were evident with most pharmacological interventions. Although data extraction from reviews was optimised when more than one review reported data for the same RCT, the reliability of the data extraction within these reviews cannot be guaranteed by this assessment report. Several interventions significantly improved IELT. Many interventions also improved sexual satisfaction and other outcomes. However, assessment of longer-term safety and effectiveness is required to evaluate whether or not initial treatment effects are maintained long term, whether or not dose escalation is required, how

  19. Health care resource use and direct medical costs for patients with schizophrenia in Tianjin, People’s Republic of China

    Directory of Open Access Journals (Sweden)

    Wu J

    2015-04-01

    Full Text Available Jing Wu,1 Xiaoning He,1 Li Liu,2 Wenyu Ye,2 William Montgomery,3 Haibo Xue,2 Jeffery S McCombs41School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, People’s Republic of China; 2Lilly Suzhou Pharmaceutical Company, Ltd, Shanghai, People’s Republic of China; 3Eli Lilly and Company, Sydney, Australia; 4Departments of Clinical Pharmacy and Pharmaceutical Economics and Policy, School of Pharmacy, University of Southern California, Los Angeles, CA, USAObjective: Information concerning the treatment costs of schizophrenia is scarce in People’s Republic of China. The aims of this study were to quantify health care resource utilization and to estimate the direct medical costs for patients with schizophrenia in Tianjin, People’s Republic of China.Methods: Data were obtained from the Tianjin Urban Employee Basic Medical Insurance (UEBMI database. Adult patients with ≥1 diagnosis of schizophrenia and 12-month continuous enrollment after the first schizophrenia diagnosis between 2008 and 2009 were included. Both schizophrenia-related, psychiatric-related, and all-cause related resource utilization and direct medical costs were estimated.Results: A total of 2,125 patients were included with a mean age of 52.3 years, and 50.7% of the patients were female. The annual mean all-cause costs were $2,863 per patient with psychiatric-related and schizophrenia-related costs accounting for 84.1% and 62.0% respectively. The schizophrenia-related costs for hospitalized patients were eleven times greater than that of patients who were not hospitalized. For schizophrenia-related health services, 60.8% of patients experienced at least one hospitalization with a mean (median length of stay of 112.1 (71 days and a mean cost of $1,904 per admission; 59.0% of patients experienced at least one outpatient visit with a mean (median number of visits of 6.2 (4 and a mean cost of $42 per visit during the 12-month follow-up period. Non

  20. Online continuing medical education as a key link for successful noncommunicable disease self-management: the CASALUD™ Model

    Directory of Open Access Journals (Sweden)

    Gallardo-Rincón H

    2017-10-01

    Full Text Available Héctor Gallardo-Rincón,1 Rodrigo Saucedo-Martínez,1 Ricardo Mujica-Rosales,1 Evan M Lee,2 Amy Israel,2 Braulio Torres-Beltran,3 Úrsula Quijano-González,3 Elena Rose Atkinson,3 Pablo Kuri-Morales,4 Roberto Tapia-Conyer1 1Fundación Carlos Slim, Mexico City, Mexico; 2Lilly Global Health, Eli Lilly and Company, Vernier, Switzerland; 3C230 Consultores, Mexico City, Mexico; 4Mexican Ministry of Health, Mexico City, Mexico Purpose: The purpose of this study is to evaluate how the benefits of online continuing medical education (CME provided to health care professionals traveled along a patient “educational chain”. In this study, the educational chain begins with the influence that CME can have on the quality of health care, with subsequent influence on patient knowledge, disease self-management, and disease biomarkers. Methods: A total of 422 patients with at least one noncommunicable disease (NCD treated in eight different Mexican public health clinics were followed over 3 years. All clinics were participants in the CASALUD Model, an NCD care model for primary care, where all clinic staff were offered CME. Data were collected through a questionnaire on health care, patient disease knowledge, and self-management behaviors; blood samples and anthropometric measurements were collected to measure patient disease biomarkers. Results: Between 2013 and 2015, the indexes measuring quality of health care, patient health knowledge, and diabetes self-management activities rose moderately but significantly (from 0.54 to 0.64, 0.80 to 0.84, and 0.62 to 0.67, respectively. Performing self-care activities – including owning and using a glucometer and belonging to a disease support group – saw the highest increase (from 0.65 to 0.75. A1C levels increased between 2013 and 2015 from 7.95 to 8.41% (63–68 mmol/mol (P<0.001, and blood pressure decreased between 2014 and 2015 from 143.7/76.8 to 137.5/74.4 (systolic/diastolic reported in mmHg (P<0

  1. Treatment patterns, health care resource utilization, and costs in Japanese adults with attention-deficit hyperactivity disorder treated with atomoxetine

    Directory of Open Access Journals (Sweden)

    Imagawa H

    2018-02-01

    Full Text Available Hideyuki Imagawa,1 Saurabh P Nagar,2 William Montgomery,3 Tomomi Nakamura,1 Masayo Sato,1 Keith L Davis2 1Medical Development Unit Japan, Eli Lilly Japan K.K., Kobe, Japan; 2RTI Health Solutions, Research Triangle Park, NC, USA; 3Global Patient Outcomes and Real World Evidence, Eli Lilly Australia, NSW, Australia Objective: To describe the characteristics and medication treatment patterns of adult patients with attention-deficit/hyperactivity disorder (ADHD prescribed atomoxetine in Japan. Materials and methods: A retrospective analysis of insurance claims data was conducted using the Japan Medical Data Center database. Adults (≥18 years with ADHD who had ≥1 atomoxetine claim from January 1, 2013 to December 31, 2014, and ≥180 to ≤900 days of follow-up were included. First atomoxetine claim defined the index date. Patient characteristics included age, gender, and comorbid conditions. Treatment patterns assessed included rates of atomoxetine discontinuation, switching, persistence, adherence (assessed via the medication possession ratio, and use of concomitant medications. Results: A total of 457 adults met all the inclusion criteria. Mean (SD age was 32.7 (10.4 years, and 61.0% of patients were male. Nearly 72.0% of the patients had at least one comorbid mental health condition in the baseline period; depression (43.8% and insomnia (40.7% were the most common mental health comorbidities. Most common physical comorbidities were chronic obstructive pulmonary disease (14.4% and diabetes (12.9%. Non-ADHD-specific psychotropics were prescribed to 59.7% of patients during the baseline period and to 65.9% during the follow-up period; 6.6% were prescribed non-ADHD-specific psychotropics concomitantly with atomoxetine. Overall, 40.0% of adults discontinued atomoxetine during the entire follow-up period and 65.9% were persistent with atomoxetine therapy at 3 months post-index date. Mean (SD atomoxetine medication possession ratio was 0.57 (0

  2. Real-world hospital costs for nonchemotherapy drugs and nondrug care associated with platinum-based doublets in the first-line setting for advanced nonsquamous non-small-cell lung cancer in Chinese patients: a retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Chen JH

    2016-04-01

    Full Text Available Jianhua Chen,1 Shengqi Wu,2 Chenping Hu,3 Yicheng Yang,4 Narayan Rajan,5 Yun Chen,4 Canjuan Yang,6 Jianfeng Li,6 Wendong Chen7 1Department of Medical Oncology, 2Department of Research and Education, Hunan Province Tumor Hospital, 3Department of Respiratory, Xiangya Hospital, Central South University, Changsha, Hunan, 4Lilly Suzhou Pharmaceutical Co., Ltd. Shanghai Branch, Shanghai, People's Republic of China; 5Global Health Outcomes Research, Eli Lilly and Co, Indianapolis, IN, USA; 6Division of Health Outcome Research, Normin Health Changsha Representative Office, Changsha, Hunan, People's Republic of China; 7Normin Health, Toronto, ON, Canada Objective: The objective of this study was to compare hospital costs per treatment cycle (HCTC for nonchemotherapy drugs and nondrug care associated with platinum-based doublets in the first-line setting for advanced nonsquamous non-small-cell lung cancer (AdvNS-NSCLC in Chinese patients. Methods: Patients receiving platinum-based doublets in the first-line setting for AdvNS-NSCLC from 2010 to 2012 in two Chinese tertiary hospitals were identified to create the retrospective study cohort. Propensity score methods were used to create matched treatment groups for head-to-head comparisons on HCTC between pemetrexed–platinum and other platinum-based doublets. Multiple linear regression analyses were performed to rank studied platinum-based doublets for their associations with the log10 scale of HCTC for nonchemotherapy drugs and nondrug care. Results: Propensity score methods created matched treatment groups for pemetrexed–platinum versus docetaxel–platinum (61 pairs, paclitaxel–platinum (39 pairs, gemcitabine–platinum (93 pairs, and vinorelbine–platinum (73 pairs, respectively. Even though the log10 scale of HCTC for nonchemotherapy drugs and nondrug care associated with pemetrexed–platinum was ranked lowest in all patients (coefficient –0.174, P=0.015, which included patients experiencing

  3. Quantifying the chiral magnetic effect from anomalous-viscous fluid dynamics

    Science.gov (United States)

    Jiang, Yin; Shi, Shuzhe; Yin, Yi; Liao, Jinfeng

    2018-01-01

    The Chiral Magnetic Effect (CME) is a macroscopic manifestation of fundamental chiral anomaly in a many-body system of chiral fermions, and emerges as an anomalous transport current in the fluid dynamics framework. Experimental observation of the CME is of great interest and has been reported in Dirac and Weyl semimetals. Significant efforts have also been made to look for the CME in heavy ion collisions. Critically needed for such a search is the theoretical prediction for the CME signal. In this paper we report a first quantitative modeling framework, Anomalous Viscous Fluid Dynamics (AVFD), which computes the evolution of fermion currents on top of realistic bulk evolution in heavy ion collisions and simultaneously accounts for both anomalous and normal viscous transport effects. AVFD allows a quantitative understanding of the generation and evolution of CME-induced charge separation during the hydrodynamic stage, as well as its dependence on theoretical ingredients. With reasonable estimates of key parameters, the AVFD simulations provide the first phenomenologically successful explanation of the measured signal in 200 AGeV AuAu collisions. This material is based upon work supported by the U.S. Department of Energy, Office of Science, Office of Nuclear Physics, within the framework of the Beam Energy Scan Theory (BEST) Topical Collaboration. The work is also supported in part by the National Science Foundation under Grant No. PHY-1352368 (SS and JL), by the National Science Foundation of China under Grant No. 11735007 (JL) and by the U.S. Department of Energy under grant Contract Number No. DE- SC0012704 (BNL)/DE-SC0011090 (MIT) (YY). JL is grateful to the Institute for Nuclear Theory for hospitality during the INT-16-3 Program. The computation of this research was performed on IU’s Big Red II cluster, supported in part by Lilly Endowment, Inc. (through its support for the Indiana University Pervasive Technology Institute) and in part by the Indiana METACyt

  4. Effects of Resolution on the Simulation of Boundary-layer Clouds and the Partition of Kinetic Energy to Subgrid Scales

    Directory of Open Access Journals (Sweden)

    Anning Cheng

    2010-02-01

    Full Text Available Seven boundary-layer cloud cases are simulated with UCLA-LES (The University of California, Los Angeles – large eddy simulation model with different horizontal and vertical gridspacing to investigate how the results depend on gridspacing. Some variables are more sensitive to horizontal gridspacing, while others are more sensitive to vertical gridspacing, and still others are sensitive to both horizontal and vertical gridspacings with similar or opposite trends. For cloud-related variables having the opposite dependence on horizontal and vertical gridspacings, changing the gridspacing proportionally in both directions gives the appearance of convergence. In this study, we mainly discuss the impact of subgrid-scale (SGS kinetic energy (KE on the simulations with coarsening of horizontal and vertical gridspacings. A running-mean operator is used to separate the KE of the high-resolution benchmark simulations into that of resolved scales of coarse-resolution simulations and that of SGSs. The diagnosed SGS KE is compared with that parameterized by the Smagorinsky-Lilly SGS scheme at various gridspacings. It is found that the parameterized SGS KE for the coarse-resolution simulations is usually underestimated but the resolved KE is unrealistically large, compared to benchmark simulations. However, the sum of resolved and SGS KEs is about the same for simulations with various gridspacings. The partitioning of SGS and resolved heat and moisture transports is consistent with that of SGS and resolved KE, which means that the parameterized transports are underestimated but resolved-scale transports are overestimated. On the whole, energy shifts to large-scales as the horizontal gridspacing becomes coarse, hence the size of clouds and the resolved circulation increase, the clouds become more stratiform-like with an increase in cloud fraction, cloud liquid-water path and surface precipitation; when coarse vertical gridspacing is used, cloud sizes do not

  5. A breakthrough in enzyme technology to fight penicillin resistance-industrial application of penicillin amidase.

    Science.gov (United States)

    Buchholz, Klaus

    2016-05-01

    Enzymatic penicillin hydrolysis by penicillin amidase (also penicillin acylase, PA) represents a Landmark: the first industrially and economically highly important process using an immobilized biocatalyst. Resistance of infective bacteria to antibiotics had become a major topic of research and industrial activities. Solutions to this problem, the antibiotics resistance of infective microorganisms, required the search for new antibiotics, but also the development of derivatives, notably penicillin derivatives, that overcame resistance. An obvious route was to hydrolyse penicillin to 6-aminopenicillanic acid (6-APA), as a first step, for the introduction via chemical synthesis of various different side chains. Hydrolysis via chemical reaction sequences was tedious requiring large amounts of toxic chemicals, and they were cost intensive. Enzymatic hydrolysis using penicillin amidase represented a much more elegant route. The basis for such a solution was the development of techniques for enzyme immobilization, a highly difficult task with respect to industrial application. Two pioneer groups started to develop solutions to this problem in the late 1960s and 1970s: that of Günter Schmidt-Kastner at Bayer AG (Germany) and that of Malcolm Lilly of Imperial College London. Here, one example of this development, that at Bayer, will be presented in more detail since it illustrates well the achievement of a solution to the problems of industrial application of enzymatic processes, notably development of an immobilization method for penicillin amidase suitable for scale up to application in industrial reactors under economic conditions. A range of bottlenecks and technical problems of large-scale application had to be overcome. Data giving an inside view of this pioneer achievement in the early phase of the new field of biocatalysis are presented. The development finally resulted in a highly innovative and commercially important enzymatic process to produce 6-APA that

  6. Simulation of turbulent flow over staggered tube bundles using multi-relaxation time lattice Boltzmann method

    International Nuclear Information System (INIS)

    Park, Jong Woon; Choi, Hyun Gyung

    2014-01-01

    A turbulent fluid flow over staggered tube bundles is of great interest in many engineering fields including nuclear fuel rods, heat exchangers and especially a gas cooled reactor lower plenum. Computational methods have evolved for the simulation of such flow for decades and lattice Boltzmann method (LBM) is one of the attractive methods due to its sound physical basis and ease of computerization including parallelization. In this study to find computational performance of the LBM in turbulent flows over staggered tubes, a fluid flow analysis code employing multi-relaxation time lattice Boltzmann method (MRT-LBM) is developed based on a 2-dimensional D2Q9 lattice model and classical sub-grid eddy viscosity model of Smagorinsky. As a first step, fundamental performance MRT-LBM is investigated against a standard problem of a flow past a cylinder at low Reynolds number in terms of drag forces. As a major step, benchmarking of the MRT-LBM is performed over a turbulent flow through staggered tube bundles at Reynolds number of 18,000. For a flow past a single cylinder, the accuracy is validated against existing experimental data and previous computations in terms of drag forces on the cylinder. Mainly, the MRT-LBM computation for a flow through staggered tube bundles is performed and compared with experimental data and general purpose computational fluid dynamic (CFD) analyses with standard k-ω turbulence and large eddy simulation (LES) equipped with turbulence closures of Smagrinsky-Lilly and wall-adapting local eddy-viscosity (WALE) model. The agreement between the experimental and the computational results from the present MRT-LBM is found to be reasonably acceptable and even comparable to the LES whereas the computational efficiency is superior. (orig.)

  7. Simulation of turbulent flow over staggered tube bundles using multi-relaxation time lattice Boltzmann method

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jong Woon; Choi, Hyun Gyung [Dongguk Univ., Gyeongju (Korea, Republic of). Nuclear and Energy Engineering Dept.

    2014-02-15

    A turbulent fluid flow over staggered tube bundles is of great interest in many engineering fields including nuclear fuel rods, heat exchangers and especially a gas cooled reactor lower plenum. Computational methods have evolved for the simulation of such flow for decades and lattice Boltzmann method (LBM) is one of the attractive methods due to its sound physical basis and ease of computerization including parallelization. In this study to find computational performance of the LBM in turbulent flows over staggered tubes, a fluid flow analysis code employing multi-relaxation time lattice Boltzmann method (MRT-LBM) is developed based on a 2-dimensional D2Q9 lattice model and classical sub-grid eddy viscosity model of Smagorinsky. As a first step, fundamental performance MRT-LBM is investigated against a standard problem of a flow past a cylinder at low Reynolds number in terms of drag forces. As a major step, benchmarking of the MRT-LBM is performed over a turbulent flow through staggered tube bundles at Reynolds number of 18,000. For a flow past a single cylinder, the accuracy is validated against existing experimental data and previous computations in terms of drag forces on the cylinder. Mainly, the MRT-LBM computation for a flow through staggered tube bundles is performed and compared with experimental data and general purpose computational fluid dynamic (CFD) analyses with standard k-ω turbulence and large eddy simulation (LES) equipped with turbulence closures of Smagrinsky-Lilly and wall-adapting local eddy-viscosity (WALE) model. The agreement between the experimental and the computational results from the present MRT-LBM is found to be reasonably acceptable and even comparable to the LES whereas the computational efficiency is superior. (orig.)

  8. Lattice Boltzmann simulation of flow across a staggered tube bundle array

    Energy Technology Data Exchange (ETDEWEB)

    Tiftikçi, A.; Kocar, C., E-mail: ckocar@hacettepe.edu.tr

    2016-04-15

    Highlights: • Large eddy simulation of the cross-flow in a staggered tube bundle array in 3D was made. • LBM and FVM are used separately as numerical solvers and the results of each method compared with experimental data. • Effect of lattice model is studied for tube bundle flow. • Filter size effects, mesh size effects are studied for VLES turbulence model. - Abstract: The decision on the magnitude of the grid size is a crucial problem in large eddy simulations. Finer mesh requires excessive memory and causes long simulation time. Large eddy simulation model becomes inefficient when the extent of the flow geometry to be simulated with the lattice-Boltzmann method is large. Thus, in this study, it is proposed to investigate the capabilities of three turbulence models, namely, very large eddy simulation, Van Driest and Smagorinsky–Lilly. As a test case, a staggered tube bundle flow experiment is used for the validation and comparison purposes. Sensitivity analyses (including mesh and filter size) have been made. Furthermore, the effect of lattice model is investigated and it is showed that the D3Q27 and D3Q19 models do not differ significantly in lattice-Boltzmann method for this type of flow. The results of turbulence model comparisons for staggered tube bundle flow showed that very large eddy simulation is superior at low resolution. This paper might be considered as a good validation of the lattice-Boltzmann method. In turbulent flow conditions, the code successfully captures the velocity and stress profiles even if the flow is quite complicated.

  9. Must Star-forming Galaxies Rapidly Get Denser before They Quench?

    Science.gov (United States)

    Abramson, L. E.; Morishita, T.

    2018-05-01

    Using the deepest data yet obtained, we find no evidence preferring compaction-triggered quenching—where rapid increases in galaxy density truncate star formation—over a null hypothesis in which galaxies age at constant surface density ({{{Σ }}}e\\equiv {M}* /2π {r}e2). Results from two fully empirical analyses and one quenching-free model calculation support this claim at all z ≤ 3: (1) qualitatively, galaxies’ mean U–V colors at 6.5 ≲ {log}{{{Σ }}}e/{\\text{}}{M}ȯ {kpc}}-2≲ 10 have reddened at rates/times correlated with {{{Σ }}}e, implying that there is no density threshold at which galaxies turn red but that {{{Σ }}}e sets the pace of maturation; (2) quantitatively, the abundance of {log}{M}* /{\\text{}}{M}ȯ ≥slant 9.4 red galaxies never exceeds that of the total population a quenching time earlier at any {{{Σ }}}e, implying that galaxies need not transit from low to high densities before quenching; (3) applying d{log}{r}e/{dt}=1/2 d{log}{M}* /{dt} to a suite of lognormal star formation histories reproduces the evolution of the size–mass relation at {log}{M}* /{\\text{}}{M}ȯ ≥slant 10. All results are consistent with evolutionary rates being set ab initio by global densities, with denser objects evolving faster than less-dense ones toward a terminal quiescence induced by gas depletion or other ∼Hubble-timescale phenomena. Unless stellar ages demand otherwise, observed {{{Σ }}}e thresholds need not bear any physical relation to quenching beyond this intrinsic density–formation epoch correlation, adding to Lilly & Carollo’s arguments to that effect.

  10. Following the results of the EMPA-REG OUTCOME trial with empagliflozin, is it possible to speak of a class effect?

    Directory of Open Access Journals (Sweden)

    Ampudia-Blasco FJ

    2017-01-01

    Full Text Available Francisco Javier Ampudia‑Blasco,1 Irene Romera,2 Bernat Ariño,3 Ramón Gomis4 1Endocrinology and Nutrition Department, Clinic University Hospital Valencia, Valencia, Spain; 2Eli Lilly and Company España, Madrid, Spain; 3Boehringer Ingelheim España, Barcelona, Spain; 4Endocrinology Department, Hospital Clinic Barcelona, Barcelona, Spain Background: The recently published cardiovascular outcomes data for the first sodium–glucose cotransporter 2 (SGLT2 inhibitor, empagliflozin, have shown cardiovascular safety and additional benefits in patients with type 2 diabetes and established cardiovascular disease. Empagliflozin showed lower rates of death from cardiovascular causes or from any causes and lower hospitalization rates from heart failure compared with placebo, both in addition to standard care. This commentary discusses the existence of a possible class effect considering the available evidence described for other SGLT2 inhibitors. Main text: Empagliflozin, dapagliflozin and canagliflozin share the same mechanism of action, and it is a plausible hypothesis that some of the benefits of empagliflozin treatment could also be expected from other SGLT2 inhibitors. However, the rapid and persistent occurrence of cardiovascular benefits observed with empagliflozin and the different results shown by the three inhibitors in meta-analyses of some of their respective Phase II and III trials might suggest another possible mechanism of action, perhaps related to the different selectivity to inhibit SGLT-2 and other SGLT family members that these compounds present. Conclusion: There is still lack of evidence to answer whether the cardiovascular benefits observed with empagliflozin in the EMPA-REG OUTCOME study could be seen as a “class effect”, which is also attributable to dapagliflozin and canagliflozin. Keywords: cardiovascular, outcome studies, SGLT2 inhibitors, empagliflozin, dapagliflozin, canagliflozin

  11. A six-month double-blind, placebo-controlled, randomized clinical trial of duloxetine for the treatment of fibromyalgia

    Directory of Open Access Journals (Sweden)

    Amy S Chappell

    2008-12-01

    Full Text Available Amy S Chappell1, Laurence A Bradley2, Curtis Wiltse1, Michael J Detke1,3,4, Deborah N D’Souza1, Michael Spaeth51Lilly Research Laboratories, Indianapolis, IN, USA; 2University of Alabama at Birmingham, Birmingham, Alabama, USA; 3Indiana University School of Medicine, Indianapolis, IN, USA; 4Harvard Medical School, Boston, MA, USA; 5Practice for Internal Medicine/Rheumatology, Graefelfing, GermanyObjective: Assess the efficacy of duloxetine 60/120 mg (N = 162 once daily compared with placebo (N = 168 in the treatment of patients with fibromyalgia, during six months of treatment.Methods: This was a phase-III, randomized, double-blind, placebo-controlled, parallel-group study assessing the efficacy and safety of duloxetine.Results: There were no significant differences between treatment groups on the co-primary efficacy outcome measures, change in the Brief Pain Inventory (BPI average pain severity from baseline to endpoint (P = 0.053 and the Patient’s Global Impressions of Improvement (PGI-I at endpoint (P = 0.073. Duloxetine-treated patients improved significantly more than placebo-treated patients on the Fibromyalgia Impact Questionnaire pain score, BPI least pain score and average interference score, Clinical Global Impressions of Severity scale, area under the curve of pain relief, Multidimensional Fatigue Inventory mental fatigue dimension, Beck Depression Inventory-II total score, and 36-item Short Form Health Survey mental component summary and mental health score. Nausea was the most common treatment-emergent adverse event in the duloxetine group. Overall discontinuation rates were similar between groups.Conclusions: Although duloxetine 60/120 mg/day failed to demonstrate significant improvement over placebo on the co-primary outcome measures, in this supportive study, duloxetine demonstrated significant improvement compared with placebo on numerous secondary measures.Keywords: fibromyalgia, duloxetine, placebo, double-blind, trial

  12. Factors Associated with Adherence to and Treatment Duration of Erlotinib Among Patients with Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Hess, Lisa M; Louder, Anthony; Winfree, Katherine; Zhu, Yajun E; Oton, Ana B; Nair, Radhika

    2017-06-01

    In lung cancer, there is an increasing number of oral agents available for patients; however, little is known about the factors associated with adherence to and treatment duration on oral medications in non-small cell lung cancer (NSCLC). To evaluate the clinical and demographic factors associated with adherence and treatment discontinuation, respectively, to oral oncolytics among patients with NSCLC. A retrospective, claims-based analysis of the Humana Research Database supplemented with medical chart review was conducted among patients with NSCLC who started an oral oncolytic between January 1, 2008, and June 30, 2013. Patients were required to be enrolled at least 1 year before the start of oral oncolytics and have no evidence of any oral oncolytic use during this period. Logistic regression models and Cox proportional hazard models were used to identify predictors associated with medication adherence and treatment duration, respectively. Among all oral oncolytics, only the cohort starting on erlotinib had sufficient sample size (n = 1,452). A wide variety of factors were found to be associated with adherence. Low-income subsidy status, previous use of intravenous chemotherapy, and lower total baseline health care costs were significantly related to decreasing adherence (each P cost was associated with decreasing adherence to erlotinib (P costs (P Company to Comprehensive Health Insights, a Humana company, as a collaborative research project involving employees of both companies. Hess, Winfree, Zhu, and Oton are employees of Eli Lilly and Company. Louder and Nair are employees of Comprehensive Health Insights, which received funding to complete this research. Study concept and design were contributed by Hess, Zhu, Winfree, and Oton. Nair and Louder collected the data, and data interpretation was performed by all the authors. The manuscript was written primarily by Hess, along with Nair, and revised by Hess, Nair, Louder, and Winfree, with assistance from Zhu and

  13. The effects of atomoxetine on emotional control in adults with ADHD: An integrated analysis of multicenter studies.

    Science.gov (United States)

    Asherson, P; Stes, S; Nilsson Markhed, M; Berggren, L; Svanborg, P; Kutzelnigg, A; Deberdt, W

    2015-06-01

    To investigate the effects of atomoxetine on emotional control in adults with ADHD. We performed an integrated analysis using individual patient data pooled from three Eli Lilly-sponsored studies. An integrated analysis can be viewed as a meta-analysis of individual patient-level data, rather than study-level summary data. Two populations were identified: a large sample of patients with pre-treatment baseline data (the "overall population"; n=2846); and a subset of these patients with placebo-controlled efficacy data from baseline to 10 or 12 weeks after initiating treatment (the "placebo-controlled population"; n=829). At baseline, in the overall population, ∼50% of ADHD patients had BRIEF-AS (Behavior Rating Inventory of Executive Function-Adult Version Self-Report) Emotional control subscores between 21 and 30, compared with ∼10% of normative subjects in the BRIEF-A manual. At endpoint, in the placebo-controlled population, atomoxetine led to a small (effect size 0.19) but significant (P=0.013) treatment effect for emotional control. The effect size was 0.32 in patients with BRIEF-AS Emotional control scores>20 at baseline. Improvements in emotional control correlated with improvements in the core ADHD symptoms and quality-of-life. As deficient emotional control is associated with impaired social, educational and occupational functioning over and above that explained by core ADHD symptoms alone, improvements in emotional control may be clinically relevant. At baseline, adults with ADHD were more likely to have impaired emotional control than normative subjects. In the adult ADHD patients, atomoxetine treatment was associated with improvements in emotional control, as well as in core ADHD symptoms and quality-of-life. Copyright © 2015. Published by Elsevier Masson SAS.

  14. Triplet transitions of neutral CO in the spectra of comets and the abundance of CO2 or molecules containing the CO group in comets

    International Nuclear Information System (INIS)

    Biermann, L.

    1976-03-01

    The high-dispersion spectra of comet Mrkos (1957 V) taken at Mt. Palomar by J. L. Greenstein and remeasured by A. Woszczyk contain many unidentified weak lines. The possibility that some of these lines belong to transitions between triplet levels of neutral CO molecules is investigated. Their presence would suggest excitation related to the dissociative recombination of a parent containing the CO group, which is first ionized by solar uv. Of 31 CO lines (of the Asundi and Triplet systems), 14 are masked by known or by questionably identified lines as statistically expected. Of the remaining 17, 13 coincide within a few tenths of an Angstrom with an unidentified line and 4 do not. These results are contrary to statistical expectations. (Some members of the third positive system of CO, which might be present, have not been included in the figures.) Although these figures strongly favor the identification proposed, the numbers are not large enough to support entirely the argument of a small statistical probability (0.2 percent) of the observed state. Also, the rotational structure of the CO bands for the triplet systems needs further investigation. C. F. Lillie's observations of comet Bennett (1970 II) between 1200 and 1800 A, especially of the fourth positive system of CO, seem to favor a cometary atmosphere characterized by a large relative abundance of CO 2 and/or molecules containing the CO group. A model outlined for comet Bennett at 0.8 a.u. seems to be approximately consistent with observations. The chemical aspects, however, especially need further consideration. New observations, particularly of the Cameron bands of CO, are needed to settle the questions raised

  15. The tau positron-emission tomography tracer AV-1451 binds with similar affinities to tau fibrils and monoamine oxidases.

    Science.gov (United States)

    Vermeiren, Céline; Motte, Philippe; Viot, Delphine; Mairet-Coello, Georges; Courade, Jean-Philippe; Citron, Martin; Mercier, Joël; Hannestad, Jonas; Gillard, Michel

    2018-02-01

    Lilly/Avid's AV-1451 is one of the most advanced tau PET tracers in the clinic. Although results obtained in Alzheimer's disease patients are compelling, discrimination of tracer uptake in healthy individuals and patients with supranuclear palsy (PSP) is less clear as there is substantial overlap of signal in multiple brain regions. Moreover, accurate quantification of [ 18 F]AV-1451 uptake in Alzheimer's disease may not be possible. The aim of the present study was to characterize the in vitro binding of AV-1451 to understand and identify potential off-target binding that could explain the poor discrimination observed in PSP patients. [ 3 H]AV-1451 and AV-1451 were characterized in in vitro binding assays using recombinant and native proteins/tissues from postmortem samples of controls and Alzheimer's disease and PSP patients. [ 3 H]AV-1451 binds to multiple sites with nanomolar affinities in brain homogenates and to tau fibrils isolated from Alzheimer's disease or PSP patients. [ 3 H]AV-1451 also binds with similarly high affinities in brain homogenates devoid of tau pathology. This unexpected binding was demonstrated to be because of nanomolar affinities of [ 3 H]AV-1451 for monoamine oxidase A and B enzymes. High affinity of AV-1451 for monoamine oxidase proteins may limit its utility as a tau PET tracer in PSP and Alzheimer's disease because of high levels of monoamine oxidase expression in brain regions also affected by tau deposition, especially if monoamine oxidase levels change over time or with a treatment intervention. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

  16. [Psychomotor reaction in primates placed in ballistic flight in rockets].

    Science.gov (United States)

    Grandpierre, R; Chatelier, G

    1968-01-01

    Psychomotor reactions have been studied in Nemestrina Macaques during flights in rockets in which there were periods of weightlessness lasting about 10 minutes. The animals had undergone motor conditioning and responded to a light signal by pressing on a button placed on a panel where there were four other undifferentiated buttons. The lighting of the panel and pressing on the different buttons in reply was recorded with respect to time. Movement was observed by film recording, and electrical activity of the brain was kept under observation by six different recordings of the cortex. Activity of stretching and bending muscles of the legs was recorded, as well as breathing, and heart activity was recorded on an electrocardiogram. These psychological parameters were transmitted to the earth by long-distance measurement during the entire flight. The recordings made it possible to confirm that the absence of the sensation of weight seems to reduce the alertness of the animals. This fact had already been observed in Wistar's rat and cat. The sensor-psychomotor responses undergo important individual variations and depend on the motivation of the subjects. A very well motivated one reacted after a short period of adaption, as it did in the laboratory: one that was much less motivated would not work until after weightlessness has ended, and showed signs of drowsiness. These observations made during the flights in rockets confirm those of Chambers et al., Harris et al., Lilly et al. made in immersion studies; they show the important role of weight in maintaining alertness, but that changes of psychomotor activity are particularly related to motivation.

  17. Olaratumab in Combination with Doxorubicin for the Treatment of Advanced Soft Tissue Sarcoma: An Evidence Review Group Perspective of a National Institute for Health and Care Excellence Single Technology Appraisal.

    Science.gov (United States)

    Tikhonova, Irina A; Jones-Hughes, Tracey; Dunham, James; Warren, Fiona C; Robinson, Sophie; Stephens, Peter; Hoyle, Martin

    2018-01-01

    The manufacturer of olaratumab (Lartruvo ® ), Eli Lilly & Company Limited, submitted evidence for the clinical and cost effectiveness of this drug, in combination with doxorubicin, for untreated advanced soft tissue sarcoma (STS) not amenable to surgery or radiotherapy, as part of the National Institute for Health and Care Excellence (NICE) Single Technology Appraisal process. The Peninsula Technology Assessment Group, commissioned to act as the Evidence Review Group (ERG), critically reviewed the company's submission. Clinical effectiveness evidence for the company's analysis was derived from an open-label, randomised controlled trial, JGDG. The analysis was based on a partitioned survival model with a time horizon of 25 years, and the perspective was of the UK National Health Service (NHS) and Personal Social Services. Costs and benefits were discounted at 3.5% per year. Given the available evidence, olaratumab is likely to meet NICE's end-of-life criteria. To improve the cost effectiveness of olaratumab, the company offered a discount through a Commercial Access Agreement (CAA) with the NHS England. When the discount was applied, the mean base-case and probabilistic incremental cost-effectiveness ratios (ICERs) for olaratumab plus doxorubicin versus the standard-of-care doxorubicin were £46,076 and £47,127 per quality-adjusted life-year (QALY) gained, respectively; the probability of this treatment being cost effective at the willingness-to-pay threshold of £50,000 per QALY gained, applicable to end-of-life treatments, was 0.54. The respective ICERs from the ERG's analysis were approximately £60,000/QALY gained, and the probability of the treatment being cost effective was 0.21. In August 2017, the NICE Appraisal Committee recommended olaratumab in combination with doxorubicin for this indication for use via the UK Cancer Drugs Fund under the agreed CAA until further evidence being collected in the ongoing phase III trial-ANNOUNCE-becomes available in

  18. Patterns of long-term and short-term responses in adult patients with attention-deficit/hyperactivity disorder in a completer cohort of 12 weeks or more with atomoxetine.

    Science.gov (United States)

    Sobanski, E; Leppämäki, S; Bushe, C; Berggren, L; Casillas, M; Deberdt, W

    2015-11-01

    Atomoxetine is a well-established pharmacotherapy for adult ADHD. Long-term studies show incremental reductions in symptoms over time. However, clinical experience suggests that patients differ in their response patterns. From 13 Eli Lilly-sponsored studies, we pooled and analyzed data for adults with ADHD who completed atomoxetine treatment at long-term (24 weeks; n=1443) and/or short-term (12 weeks; n=2830) time-points, and had CAARS-Inv:SV total and CGI-S data up to or after these time-points and at Week 0 (i.e. at baseline, when patients first received atomoxetine). The goal was to identify and describe distinct trajectories of response to atomoxetine using hierarchical clustering methods and linear mixed modelling. Based on the homogeneity of changes in CAARS-Inv:SV total scores, 5 response clusters were identified for patients who completed long-term (24 weeks) treatment with atomoxetine, and 4 clusters were identified for patients who completed short-term (12 weeks) treatment. Four of the 5 long-term clusters (comprising 95% of completer patients) showed positive trajectories: 2 faster responding clusters (L1 and L2), and 2 more gradually responding clusters (L3 and L4). Responses (i.e.≥30% reduction in CAARS-Inv:SV total score, and CGI-S score≤3) were observed at 8 and 24 weeks in 80% and 95% of completers in Cluster L1, versus 5% and 48% in Cluster L4. While many adults with ADHD responded relatively rapidly to atomoxetine, others responded more gradually without a clear plateau at 24 weeks. Longer-term treatment may be associated with greater numbers of responders. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  19. Baricitinib in Patients with Rheumatoid Arthritis and an Inadequate Response to Conventional Disease-Modifying Antirheumatic Drugs in United States and Rest of World: A Subset Analysis.

    Science.gov (United States)

    Wells, Alvin F; Greenwald, Maria; Bradley, John D; Alam, Jahangir; Arora, Vipin; Kartman, Cynthia E

    2018-06-01

    This article evaluates the efficacy and safety of baricitinib 4 mg versus placebo in United States including Puerto Rico (US) and rest of the world (ROW) subpopulations using data pooled from RA-BEAM and RA-BUILD, which enrolled patients with moderate-to-severe adult-onset rheumatoid arthritis (RA). In RA-BEAM, patients with an inadequate response (IR) to methotrexate, at least one X-ray erosion, and high sensitivity C-reactive protein (hsCRP) ≥ 6 mg/L were randomized to placebo or orally administered baricitinib 4 mg daily or subcutaneously administered adalimumab 40 mg every other week. In RA-BUILD, patients with an IR to at least one conventional synthetic disease-modifying antirheumatic drug (csDMARD) and with hsCRP ≥ 3.6 mg/L were randomized to placebo or baricitinib 2 or 4 mg daily. Patients in both trials were biologic naive. In this post hoc analysis, data from both studies were pooled (714 baricitinib 4 mg-treated, 716 placebo-treated patients). Overall, 188 US and 1242 ROW patients were included. Subgroups differed in baseline characteristics including race, weight, age, time since RA diagnosis, current corticosteroid use, and previous csDMARD use. At weeks 12 and 24, baricitinib-treated patients had larger responses compared to placebo-treated patients for multiple efficacy outcomes: American College of Rheumatology 20/50/70 response, low disease activity, remission, Disease Activity Score 28-C-reactive protein, and Health Assessment Questionnaire-Disability Index. Overall, similar efficacy was observed in US and ROW subgroups with no notable safety differences between subgroups at weeks 12 or 24. Baricitinib 4 mg was efficacious compared to placebo in US and ROW subpopulations. Safety was similar between subgroups. Eli Lilly & Company and Incyte Corporation. ClinicalTrials.gov identifiers, NCT01721057; NCT01710358.

  20. Validation of three new methods for determination of metal emissions using a modified Environmental Protection Agency Method 301

    Energy Technology Data Exchange (ETDEWEB)

    Catherine A. Yanca; Douglas C. Barth; Krag A. Petterson; Michael P. Nakanishi; John A. Cooper; Bruce E. Johnsen; Richard H. Lambert; Daniel G. Bivins [Cooper Environmental Services, LLC, Portland, OR (United States)

    2006-12-15

    Three new methods applicable to the determination of hazardous metal concentrations in stationary source emissions were developed and evaluated for use in U.S. Environmental Protection Agency (EPA) compliance applications. Two of the three independent methods, a continuous emissions monitor-based method (Xact) and an X-ray-based filter method (XFM), are used to measure metal emissions. The third method involves a quantitative aerosol generator (QAG), which produces a reference aerosol used to evaluate the measurement methods. A modification of EPA Method 301 was used to validate the three methods for As, Cd, Cr, Pb, and Hg, representing three hazardous waste combustor Maximum Achievable Control Technology (MACT) metal categories (low volatile, semivolatile, and volatile). The measurement methods were evaluated at a hazardous waste combustor (HWC) by comparing measured with reference aerosol concentrations. The QAG, Xact, and XFM met the modified Method 301 validation criteria. All three of the methods demonstrated precisions and accuracies on the order of 5%. The measurement methods should be applicable to emissions from a wide range of sources, and the reference aerosol generator should be applicable to additional analytes. EPA recently approved an alternative monitoring petition for an HWC at Eli Lilly's Tippecanoe site in Lafayette, IN, in which the Xact is used for demonstrating compliance with the HWC MACT metal emissions (low volatile, semivolatile, and volatile). The QAG reference aerosol generator was approved as a method for providing a quantitative reference aerosol, which is required for certification and continuing quality assurance of the Xact. 30 refs., 5 figs., 11 tabs.

  1. ISM EXCITATION AND METALLICITY OF STAR-FORMING GALAXIES AT Z ≃ 3.3 FROM NEAR-IR SPECTROSCOPY

    Energy Technology Data Exchange (ETDEWEB)

    Onodera, M.; Carollo, C. M.; Lilly, S.; Tacchella, S. [Institute for Astronomy, ETH Zürich, Wolfgang-Pauli-Strasse 27, 8093 Zürich (Switzerland); Renzini, A. [INAF-Osservatorio Astronomico di Padova, Vicolo dell’Osservatorio 5, I-35122, Padova (Italy); Arimoto, N. [Subaru Telescope, National Astronomical Observatory of Japan, 650 North A’ohoku Place, Hilo, HI 96720 (United States); Capak, P. [Infrared Processing and Analysis Center (IPAC), 1200 East California Boulevard, Pasadena, CA 91125 (United States); Daddi, E. [CEA, Laboratoire AIM-CNRS-Université Paris Diderot, Irfu/SAp, Orme des Merisiers, F-91191 Gif-sur-Yvette (France); Scoville, N. [California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125 (United States); Tatehora, S. [Graduate University for Advanced Studies, 2-21-1 Osawa, Mitaka, Tokyo (Japan); Zamorani, G., E-mail: monodera@phys.ethz.ch [INAF-Osservatorio Astronomico di Bologna, Via Ranzani 1, I-40127 Bologna (Italy)

    2016-05-01

    We study the relationship between stellar mass, star formation rate (SFR), ionization state, and gas-phase metallicity for a sample of 41 normal star-forming galaxies at 3 ≲ z ≲ 3.7. The gas-phase oxygen abundance, ionization parameter, and electron density of ionized gas are derived from rest-frame optical strong emission lines measured on near-infrared spectra obtained with Keck/Multi-Object Spectrograph for Infra-Red Exploration. We remove the effect of these strong emission lines in the broadband fluxes to compute stellar masses via spectral energy distribution fitting, while the SFR is derived from the dust-corrected ultraviolet luminosity. The ionization parameter is weakly correlated with the specific SFR, but otherwise the ionization parameter and electron density do not correlate with other global galaxy properties such as stellar mass, SFR, and metallicity. The mass–metallicity relation (MZR) at z ≃ 3.3 shows lower metallicity by ≃0.7 dex than that at z = 0 at the same stellar mass. Our sample shows an offset by ≃0.3 dex from the locally defined mass–metallicity–SFR relation, indicating that simply extrapolating such a relation to higher redshift may predict an incorrect evolution of MZR. Furthermore, within the uncertainties we find no SFR–metallicity correlation, suggesting a less important role of SFR in controlling the metallicity at high redshift. We finally investigate the redshift evolution of the MZR by using the model by Lilly et al., finding that the observed evolution from z = 0 to z ≃ 3.3 can be accounted for by the model assuming a weak redshift evolution of the star formation efficiency.

  2. Estimating Drug Costs: How do Manufacturer Net Prices Compare with Other Common US Price References?

    Science.gov (United States)

    Mattingly, T Joseph; Levy, Joseph F; Slejko, Julia F; Onwudiwe, Nneka C; Perfetto, Eleanor M

    2018-05-12

    Drug costs are frequently estimated in economic analyses using wholesale acquisition cost (WAC), but what is the best approach to develop these estimates? Pharmaceutical manufacturers recently released transparency reports disclosing net price increases after accounting for rebates and other discounts. Our objective was to determine whether manufacturer net prices (MNPs) could approximate the discounted prices observed by the U.S. Department of Veterans Affairs (VA). We compared the annual, average price discounts voluntarily reported by three pharmaceutical manufacturers with the VA price for specific products from each company. The top 10 drugs by total sales reported from company tax filings for 2016 were included. The discount observed by the VA was determined from each drug's list price, reported as WAC, in 2016. Descriptive statistics were calculated for the VA discount observed and a weighted price index was calculated using the lowest price to the VA (Weighted VA Index), which was compared with the manufacturer index. The discounted price as a percentage of the WAC ranged from 9 to 74%. All three indexes estimated by the average discount to the VA were at or below the manufacturer indexes (42 vs. 50% for Eli Lilly, 56 vs. 65% for Johnson & Johnson, and 59 vs. 59% for Merck). Manufacturer-reported average net prices may provide a close approximation of the average discounted price granted to the VA, suggesting they may be a useful proxy for the true pharmacy benefits manager (PBM) or payer cost. However, individual discounts for products have wide variation, making a standard discount adjustment across multiple products less acceptable.

  3. Cost Analyses in the US and Japan: A Cross-Country Comparative Analysis Applied to the PRONOUNCE Trial in Non-Squamous Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Hess, Lisa M; Rajan, Narayan; Winfree, Katherine; Davey, Peter; Ball, Mark; Knox, Hediyyih; Graham, Christopher

    2015-12-01

    Health technology assessment is not required for regulatory submission or approval in either the United States (US) or Japan. This study was designed as a cross-country evaluation of cost analyses conducted in the US and Japan based on the PRONOUNCE phase III lung cancer trial, which compared pemetrexed plus carboplatin followed by pemetrexed (PemC) versus paclitaxel plus carboplatin plus bevacizumab followed by bevacizumab (PCB). Two cost analyses were conducted in accordance with International Society For Pharmacoeconomics and Outcomes Research good research practice standards. Costs were obtained based on local pricing structures; outcomes were considered equivalent based on the PRONOUNCE trial results. Other inputs were included from the trial data (e.g., toxicity rates) or from local practice sources (e.g., toxicity management). The models were compared across key input and transferability factors. Despite differences in local input data, both models demonstrated a similar direction, with the cost of PemC being consistently lower than the cost of PCB. The variation in individual input parameters did affect some of the specific categories, such as toxicity, and impacted sensitivity analyses, with the cost differential between comparators being greater in Japan than in the US. When economic models are based on clinical trial data, many inputs and outcomes are held consistent. The alterable inputs were not in and of themselves large enough to significantly impact the results between countries, which were directionally consistent with greater variation seen in sensitivity analyses. The factors that vary across jurisdictions, even when minor, can have an impact on trial-based economic analyses. Eli Lilly and Company.

  4. Comparison of standard (self-directed) versus intensive patient training for the human insulin inhalation powder (HIIP) delivery system in patients with type 2 diabetes: efficacy, safety, and training measures.

    Science.gov (United States)

    Rosenstock, Julio; Nakano, Masako; Silverman, Bernard L; Sun, Bin; de la Peña, Amparo; Suri, Ajit; Muchmore, Douglas B

    2007-02-01

    The Lilly/Alkermes human insulin inhalation powder (HIIP) delivery system [AIR (a registered trademark of Alkermes, Inc., Cambridge, MA) Inhaled Insulin System] was designed to be easy to use. Training methods were compared in insulin-naive patients with type 2 diabetes. Patients (n = 102) were randomized to standard or intensive training. With standard training, patients learned how to use the HIIP delivery system by reading directions for use (DFU) and trying on their own. Intensive training included orientation to the HIIP delivery system with individual coaching and inspiratory flow rate training. Both groups received preprandial HIIP + metformin with or without a thiazolidinedione for 4 weeks. Overall 2-h postprandial blood glucose (PPBG) excursion was the primary measure. Noninferiority was defined as the upper limit of the two-sided 95% confidence interval of the mean difference between groups being 1.2 training) and 0.23 +/- 0.36 (intensive training) mmol/L. The mean difference (standard minus intensive training) and two-sided 95% confidence interval were -0.35 (-1.02, 0.33) mmol/L. No statistically or clinically significant differences were observed between training methods in premeal, postmeal, or bedtime blood glucose values, HIIP doses at endpoint, or blood glucose values after a test meal. No discontinuations occurred because of difficulty of use or dislike of the HIIP system. DFU compliance was >90% in both training groups. There were no significant differences between training methods in safety measures. The HIIP delivery system is easy to use, and most patients can learn to use it by reading the DFU without assistance from health care professionals.

  5. Assessing the effect of weight and weight loss in obese persons with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Bradley Curtis

    2008-10-01

    Full Text Available Bradley Curtis1, Risa P Hayes1, Sheri Fehnel2, Laurie Zografos21Global Health Outcomes, Eli Lilly and Co, Indianapolis, IN, USA; 2RTI Health Solutions, Research Triangle Park, NC, USAAbstract: The objective of this study was to assess specific areas of life in which obesity affects individuals with type 2 diabetes mellitus (T2DM, and changes that obese persons with T2DM experience with weight loss of varying degrees. Thirty in-depth interviews were conducted in persons identified as: age ≥40 years, diagnosed with T2DM for ≥2 years, on oral antihyperglycemic medications >3 months, BMI 30–35 kg/m2, having attempted to lose weight in the last 2 years. Participants (60% female, mean age 53 years, 53% Caucasian, mean BMI 32.2 kg/m2 agreed that 5% weight loss, while not reflective of an ultimate goal, would be meaningful and important; benefits were expected to accrue in physical functioning, self-confidence, blood glucose levels, and motivation to keep losing weight. Participants reported the greatest effect of weight loss on energy, physical activity, mobility, pain, and clothes/appearance. Participants reported weight affecting mood, with feelings of depression and frustration most commonly described. This research indicates that weight loss is likely to affect health-related quality of life in obese individuals with T2DM. Given the purported weight loss benefits of many emerging diabetic medications, it will be important to include measures of weight-related quality of life in future clinical trials of these agents.Keywords: health-related quality of life, obesity, type 2 diabetes, weight loss, patient-reported outcomes

  6. FIRST LEGO League Kickoff

    Science.gov (United States)

    2007-01-01

    Randall Hicks (right), Jacobs Technology's Education Services manager at NASA John C. Stennis Space Center, answers questions about the playing field for FIRST (For Inspiration and Recognition of Science and Technology) LEGO League's 2007 Challenge, `Power Puzzle.' More than 140 teachers, mentors, parents and students from 15 schools attended the Sept. 15 FLL season kickoff at StenniSphere, the visitor center at SSC. The teams from southern and central Mississippi and Mobile, Ala., who came to SSC heard rules for and asked questions about `Power Puzzle,' and saw robot demonstrations by Gulfport and Picayune high schools' past FIRST Robotics competitions. Using LEGO Mindstorms NXT kits, FLL teams of children ages 9-14 will spend the next three months building and programming robots to perform 'Power Puzzle's' challenge tasks, then pit them in competitions. They also will submit a research project about how energy choices impact the environment and the economy. The season will culminate at the Mississippi Championship Tournament on Dec. 8 at the Mississippi Gulf Coast Community College. FLL, considered the `little league' of the FIRST Robotics Competition, partners FIRST and the LEGO Group. Competitions aim to inspire and celebrate science and technology using real-world context and hands-on experimentation. NASA recognizes FIRST activities as an excellent hands-on method to increase student knowledge of science, engineering, technology and mathematics. Schools represented in this year's kickoff were: Madison Avenue Upper Elementary, the Mississippi Band of Choctaw Indians' Conehatta Elementary, Hattiesburg's Lillie Burney Elementary, Pearl Upper Elementary, Long Beach Middle, Oktibehha Elementary, d'Iberville Middle, Saucier's West Wortham Middle, Picayune's Nicholson Elementary and Roseland Park Baptist Church Academy, Bay St. Louis' St. Stanislaus College and Mobile's Davidson High, as well as two home-school groups from the Jackson area.

  7. Adherence to Basal Insulin Therapy Among People with Type 2 Diabetes: A Retrospective Cohort Study of Costs and Patient Outcomes.

    Science.gov (United States)

    Perez-Nieves, Magaly; Boye, Kristina S; Kiljanski, Jacek; Cao, Dachung; Lage, Maureen J

    2018-04-11

    This research compares costs, resource utilization, and complications between adherent and nonadherent patients over the 3-year period post initiation on basal insulin therapy. The study utilized the US-based Truven Health MarketScan ® Research Databases from 2011 through 2015. Adults aged 18 years or older and identified with type 2 diabetes (T2D) who initiated therapy on basal insulin in 2012 were included. Patients were excluded if they were pregnant, filled their index basal insulin prescription via mail order, or were not continuously insured from 1 year before through 3 years following initiation of treatment with basal insulin. Instrumental variables were used to control for selection bias, and multivariable analyses were used to examine the associations between adherence to basal insulin therapy and costs, resource utilization, and acute complications. A total of 21,363 individuals were included in the study. Three years after initiating therapy on basal insulin, patients who were adherent over time to basal insulin treatment therapy (33.8% of patients) had significantly higher diabetes-related drug costs. However, patients' adherence was associated with significantly lower diabetes-related outpatient, acute care, and total costs. Results for all-cause costs were similar. Adherent patients also had significantly fewer all-cause and diabetes-related hospitalizations and emergency room visits and were significantly less likely to be diagnosed with an acute complication. Results of this study illustrate that despite higher drug costs, there are disease-specific and all-cause cost offsets and improved patient outcomes associated with adherence to basal insulin therapy for people with T2D. Eli Lilly and Company.

  8. Cost minimization analysis of different growth hormone pen devices based on time-and-motion simulations

    Directory of Open Access Journals (Sweden)

    Kim Jaewhan

    2010-04-01

    Full Text Available Abstract Background Numerous pen devices are available to administer recombinant Human Growth Hormone (rhGH, and both patients and health plans have varying issues to consider when selecting a particular product and device for daily use. Therefore, the present study utilized multi-dimensional product analysis to assess potential time involvement, required weekly administration steps, and utilization costs relative to daily rhGH administration. Methods Study objectives were to conduct 1 Time-and-Motion (TM simulations in a randomized block design that allowed time and steps comparisons related to rhGH preparation, administration and storage, and 2 a Cost Minimization Analysis (CMA relative to opportunity and supply costs. Nurses naïve to rhGH administration and devices were recruited to evaluate four rhGH pen devices (2 in liquid form, 2 requiring reconstitution via TM simulations. Five videotaped and timed trials for each product were evaluated based on: 1 Learning (initial use instructions, 2 Preparation (arrange device for use, 3 Administration (actual simulation manikin injection, and 4 Storage (maintain product viability between doses, in addition to assessment of steps required for weekly use. The CMA applied micro-costing techniques related to opportunity costs for caregivers (categorized as wages, non-drug medical supplies, and drug product costs. Results Norditropin® NordiFlex and Norditropin® NordiPen (NNF and NNP, Novo Nordisk, Inc., Bagsværd, Denmark took less weekly Total Time (p ® Pen (GTP, Pfizer, Inc, New York, New York or HumatroPen® (HTP, Eli Lilly and Company, Indianapolis, Indiana. Time savings were directly related to differences in new package Preparation times (NNF (1.35 minutes, NNP (2.48 minutes GTP (4.11 minutes, HTP (8.64 minutes, p Conclusions Time-and-motion simulation data used to support a micro-cost analysis demonstrated that the pen device with the greater time demand has highest net costs.

  9. The Development of a Patient-Reported Outcome Measure for Assessment of Genital Psoriasis Symptoms: The Genital Psoriasis Symptoms Scale (GPSS).

    Science.gov (United States)

    Gottlieb, Alice B; Kirby, Brian; Ryan, Caitriona; Naegeli, April N; Burge, Russel; Potts Bleakman, Alison; Anatchkova, Milena D; Yosipovitch, Gil

    2018-03-01

    Patient-reported outcome measures (PROs) specific for genital psoriasis (GenPs) have not been described. In this cross-sectional, qualitative study in patients with moderate-to-severe GenPs, we sought to develop a PRO useful for GenPs symptom assessment. A literature review was performed to identify relevant psoriasis or GenPs symptoms and existing PROs that may be useful in the evaluation of symptom severity in GenPs patients. The literature review findings were discussed with clinicians, and then patients with GenPs. Relevant psoriasis or GenPs symptoms from the literature review included itch, pain, scaling, redness/erythema, and stinging/burning. The validity of these symptoms for GenPs and potentially relevant PROs was corroborated by clinical experts. After gap analysis, a draft symptom scale consisting of Numeric Rating Scale (NRS) items was constructed. We then conducted interviews with GenPs patients (n = 20) to support content validity and use of the draft symptom NRS items in routine practice and in clinical trials. Participants identified and confirmed relevant symptoms and evaluated the utility of the draft PRO. A new PRO was developed: the Genital Psoriasis Symptoms Scale (GPSS). Cognitive debriefing and cultural adaptation/translation interviews with a second group of patients confirmed cultural appropriateness of the GPSS. The GPSS may be useful for assessing symptoms before, during, and after treatment in routine clinical practice and in clinical trials involving patients with GenPs. Eli Lilly & Company. Plain language summary available for this article.

  10. A Review of Basal-Bolus Therapy Using Insulin Glargine and Insulin Lispro in the Management of Diabetes Mellitus.

    Science.gov (United States)

    Candido, Riccardo; Wyne, Kathleen; Romoli, Ester

    2018-04-13

    Basal-bolus therapy (BBT) refers to the combination of a long-acting basal insulin with a rapid-acting insulin at mealtimes. Basal insulin glargine 100 U/mL and prandial insulin lispro have been available for many years and there is a substantial evidence base to support the efficacy and safety of these agents when they are used in BBT or basal-plus therapy for patients with type 1 or type 2 diabetes mellitus (T1DM, T2DM). With the growing availability of alternative insulins for use in such regimens, it seems timely to review the data regarding BBT with insulin glargine 100 U/mL and insulin lispro. In patients with T1DM, BBT with insulin glargine plus insulin lispro provides similar or better glycemic control and leads to less nocturnal hypoglycemia compared to BBT using human insulin as the basal and/or prandial component, and generally provides similar glycemic control and rates of severe hypoglycemia to those achieved with insulin lispro administered by continuous subcutaneous insulin infusion (CSII). Studies evaluating BBT with insulin glargine plus insulin lispro in patients with T2DM also demonstrate the efficacy and safety of these insulins. Available data suggest that BBT with insulin glargine and insulin lispro provides similar levels of efficacy and safety in pediatric and adult populations with T1DM and in adult patients and those aged more than 65 years with T2DM. These insulin preparations also appear to be safe and effective for controlling T2DM in people of different ethnicities and in patients with T1DM or T2DM and comorbidities. Eli Lilly and Company.

  11. The Development of the Genital Psoriasis Sexual Frequency Questionnaire (GenPs-SFQ) to Assess the Impact of Genital Psoriasis on Sexual Health.

    Science.gov (United States)

    Gottlieb, Alice B; Kirby, Brian; Ryan, Caitriona; Naegeli, April N; Burge, Russel; Potts Bleakman, Alison; Anatchkova, Milena D; Cather, Jennifer

    2018-03-01

    Patient-reported outcome measures (PROs) exist for psoriasis but not genital psoriasis (GenPs). This cross-sectional, qualitative study in patients with moderate-to-severe GenPs was conducted to support development of a PRO for measuring the impact of GenPs on sexual activity and to establish content validity. The impacts of GenPs were identified in a literature review. Findings from the literature review were discussed with clinicians, and then patients with GenPs were interviewed. From the literature review, 52 articles, 44 abstracts, and 41 clinical trials met predefined search criteria. Of these, 11 concepts emerged as having theoretical support for use as measurable impacts of psoriasis symptoms on patients; these concepts included sexual functioning and general health-related quality of life (HRQoL). These concepts were confirmed and expanded upon by two clinicians who routinely care for patients with GenPs. Interviews were then conducted with GenPs patients (n = 20) to discuss the impact of GenPs on their HRQoL. Eighty percent of patients reported that GenPs impacted sexual frequency. The two-item GenPs Sexual Frequency Questionnaire (GenPs-SFQ) was developed to assess limitations on sexual activity frequency because of GenPs. Cognitive debriefing with an additional 50 patients with GenPs confirmed the utility and understandability of the GenPs-SFQ. The GenPs-SFQ may have utility in clinical trials involving GenPs patients and in routine clinical practice. Eli Lilly and Company. Plain language summary available for this article.

  12. SU-E-J-134: Optimizing Technical Parameters for Using Atlas Based Automatic Segmentation for Evaluation of Contour Accuracy Experience with Cardiac Structures From NRG Oncology/RTOG 0617

    Energy Technology Data Exchange (ETDEWEB)

    Yu, J; Gong, Y; Bar-Ad, V; Giaddui, T; Galvin, J; Xiao, Y [Thomas Jefferson University, Philadelphia, PA (United States); Hu, C [NRG oncology, Philadelphia, PA (United States); Gore, E; Wheatley, M [Medical College of Wisconsin, Milwaukee, WI (United States); Witt, J; Robinson, C; Bradley, J [Washington University in St. Louis School of Medicine, St. Louis, MO (United States); Kong, F [Georgia Regents University, Augusta, GA (Georgia)

    2015-06-15

    Purpose: Accurate contour delineation is crucial for radiotherapy. Atlas based automatic segmentation tools can be used to increase the efficiency of contour accuracy evaluation. This study aims to optimize technical parameters utilized in the tool by exploring the impact of library size and atlas number on the accuracy of cardiac contour evaluation. Methods: Patient CT DICOMs from RTOG 0617 were used for this study. Five experienced physicians delineated the cardiac structures including pericardium, atria and ventricles following an atlas guideline. The consistency of cardiac structured delineation using the atlas guideline was verified by a study with four observers and seventeen patients. The CT and cardiac structure DICOM files were then used for the ABAS technique.To study the impact of library size (LS) and atlas number (AN) on automatic contour accuracy, automatic contours were generated with varied technique parameters for five randomly selected patients. Three LS (20, 60, and 100) were studied using commercially available software. The AN was four, recommended by the manufacturer. Using the manual contour as the gold standard, Dice Similarity Coefficient (DSC) was calculated between the manual and automatic contours. Five-patient averaged DSCs were calculated for comparison for each cardiac structure.In order to study the impact of AN, the LS was set 100, and AN was tested from one to five. The five-patient averaged DSCs were also calculated for each cardiac structure. Results: DSC values are highest when LS is 100 and AN is four. The DSC is 0.90±0.02 for pericardium, 0.75±0.06 for atria, and 0.86±0.02 for ventricles. Conclusion: By comparing DSC values, the combination AN=4 and LS=100 gives the best performance. This project was supported by NCI grants U24CA12014, U24CA180803, U10CA180868, U10CA180822, PA CURE grant and Bristol-Myers Squibb and Eli Lilly.

  13. Gene surfing in expanding populations.

    Science.gov (United States)

    Hallatschek, Oskar; Nelson, David R

    2008-02-01

    Large scale genomic surveys are partly motivated by the idea that the neutral genetic variation of a population may be used to reconstruct its migration history. However, our ability to trace back the colonization pathways of a species from their genetic footprints is limited by our understanding of the genetic consequences of a range expansion. Here, we study, by means of simulations and analytical methods, the neutral dynamics of gene frequencies in an asexual population undergoing a continual range expansion in one dimension. During such a colonization period, lineages can fix at the wave front by means of a "surfing" mechanism [Edmonds, C.A., Lillie, A.S., Cavalli-Sforza, L.L., 2004. Mutations arising in the wave front of an expanding population. Proc. Natl. Acad. Sci. 101, 975-979]. We quantify this phenomenon in terms of (i) the spatial distribution of lineages that reach fixation and, closely related, (ii) the continual loss of genetic diversity (heterozygosity) at the wave front, characterizing the approach to fixation. Our stochastic simulations show that an effective population size can be assigned to the wave that controls the (observable) gradient in heterozygosity left behind the colonization process. This effective population size is markedly higher in the presence of cooperation between individuals ("pushed waves") than when individuals proliferate independently ("pulled waves"), and increases only sub-linearly with deme size. To explain these and other findings, we develop a versatile analytical approach, based on the physics of reaction-diffusion systems, that yields simple predictions for any deterministic population dynamics. Our analytical theory compares well with the simulation results for pushed waves, but is less accurate in the case of pulled waves when stochastic fluctuations in the tip of the wave are important.

  14. GOLDRUSH. II. Clustering of galaxies at z ˜ 4-6 revealed with the half-million dropouts over the 100 deg2 area corresponding to 1 Gpc3

    Science.gov (United States)

    Harikane, Yuichi; Ouchi, Masami; Ono, Yoshiaki; Saito, Shun; Behroozi, Peter; More, Surhud; Shimasaku, Kazuhiro; Toshikawa, Jun; Lin, Yen-Ting; Akiyama, Masayuki; Coupon, Jean; Komiyama, Yutaka; Konno, Akira; Lin, Sheng-Chieh; Miyazaki, Satoshi; Nishizawa, Atsushi J.; Shibuya, Takatoshi; Silverman, John

    2018-01-01

    We present clustering properties from 579492 Lyman-break galaxies (LBGs) at z ˜ 4-6 over the 100 deg2 sky (corresponding to a 1.4 Gpc3 volume) identified in early data of the Hyper Suprime-Cam (HSC) Subaru Strategic Program survey. We derive angular correlation functions (ACFs) for the HSC LBGs with unprecedentedly high statistical accuracies at z ˜ 4-6, and compare them with the halo occupation distribution (HOD) models. We clearly identify significant ACF excesses in 10″ physical properties including the star formation rate (SFR), the stellar-to-halo mass ratio (SHMR), and the dark matter accretion rate (\\dot{M}_{ h}) over a wide mass range of Mh/M⊙ = 4 × 1010-4 × 1012. We find that the SHMR increases from z ˜ 4 to 7 by a factor of ˜4 at Mh ≃ 1 × 1011 M⊙ , while the SHMR shows no strong evolution in the similar redshift range at Mh ≃ 1 × 1012 M⊙ . Interestingly, we identify a tight relation of SFR/\\dot{M}_{ h}-Mh showing no significant evolution beyond 0.15 dex in this wide mass range over z ˜ 4-7. This weak evolution suggests that the SFR/\\dot{M}_{ h}-Mh relation is a fundamental relation in high-redshift galaxy formation whose star formation activities are regulated by the dark matter mass assembly. Assuming this fundamental relation, we calculate the cosmic star formation rate densities (SFRDs) over z = 0-10 (a.k.a. the Madau-Lilly plot). The cosmic SFRD evolution based on the fundamental relation agrees with the one obtained by observations, suggesting that the cosmic SFRD increase from z ˜ 10 to 4 - 2 (decrease from z ˜ 4-2 to 0) is mainly driven by the increase of the halo abundance (the decrease of the accretion rate).

  15. [The register GiViTI about the use of the drug Xigris® in the Italian intensive care units].

    Science.gov (United States)

    Rossi, Carlotta; Giardino, Michele; Crespi, Daniele; Anghileri, Abramo; Poole, Daniele; Bertolini, Guido

    2013-06-01

    The Register was aimed at monitoring the use, possible side effects, and clinical effectiveness of Xigris® - drotrecogin alfa (activated) - for the treatment of severe sepsis in Italian intensive care units (ICUs). Data collection was performed using an online web form or a specific electronic module of the software Margherita, available only for the ICUs adhering to the GiViTI. Drug purchase information available for each center was used to identify and stimulate collaboration of non-compliant centers. Several countermeasures were taken to have the largest participation. We analyzed data from 1001 patients treated in 161 ICUs between July 2003 and September 2007, corresponding to 70% of all the patients who received the drug in that period. The off-label use of the drug was frequent: 15.6% of cases before and 27.3% after the label change with the introduction of timing restrictions. Treatment was temporarily interrupted in 10%, and definitely stopped in 25% of cases, after the occurrence of adverse events, the most frequent being bleeding. Severe bleeding occurred in 3.8% of patients. Multivariable analysis, which allowed an adjusted comparison with a control group, showed that treatment increased mortality among elective-surgery patients (OR 2.79, 95%CI 1.31-5.97). The results of this study and other evidences led the European Medicines Agency (EMA) to require a confirmatory trial in 2007. In October 2011 Ely-Lilly, the producer of the drug, announced the worldwide withdrawal from the market of Xigris®, on the basis of the negative results of the confirmatory trial. The availability of purchase information is essential to carry out post-marketing drug surveillance studies, since it allows to identify and contact non-compliant centers. Actually, a representative sample of treated patients provides reliable information on the use, efficacy, and safety of the drug in daily clinical practice that could positively influence healthcare policies.

  16. Eesti autobiograafilise kirjutuse kujunemisest 18. sajandist Teise maailmasõjani. The Development of Estonian Autobiographical Writing from the 18th Century to the Second World War

    Directory of Open Access Journals (Sweden)

    Rutt Hinrikus

    2012-04-01

    Full Text Available In this article I examine the development of Estonian autobiographical writing from its first manifestations to published memoirs, and the development of life writing and its diversification. The beginnings of life writing can be traced back to Estonian folk song and Estonian incidental poetry. The Moravian Brethren movement in Estonia in the 18th century promoted the spread of canonical autobiography. The Moravian Brethren offered alternative opportunities for self-realisation for Estonians who were serfs, and were therefore popular with the people. The practice of the Moravian Brethren made use of retelling and writing about the life of the congregation members, which sometimes became suitable biographies in print, especially stories of awakening. Several manuscript biographies have survived from the Brethren times, such as the biographies of Mäletu Jaan and Mihkel Sarapuu. In addition to the history of the Moravian Brethren movement, these biographies give information about the educational situation and living conditions of the people of the time. The Estonian life writing tradition emerged within the reigning Baltic German cultural space thanks to the Estophiles among the Baltic Germans (J. H. Rosenplänter and the first Estonian men of letters; from the early 19th century we have the diary by Rosenplänter, an estophile pastor from Pärnu, and the diary by the Estonian poet, the then-student Kristjan Jaak Peterson, both in the Estonian language. Johann Voldemar Jannsen, the founder of Estonian-language journalism, kept a diary in the German language for a longer period of time; it was usual that the first Estonian intellectuals (Lilli Suburg, and others in the late 19th century wrote in German. Admittedly, the first Estonian-language life history was written by a forward-looking 19th century peasant named Märt Mitt (1833-1912, who was conscious of himself as a historical subject and gave his memoirs, begun in the 1880s, a memorable title

  17. Diagnosis and Treatment of Osteoporosis Before and After Fracture: A Side-by-Side Analysis of Commercially Insured and Medicare Advantage Osteoporosis Patients.

    Science.gov (United States)

    Weaver, Jessica; Sajjan, Shiva; Lewiecki, E Michael; Harris, Steven T

    2017-07-01

    ) in the Commercial group. Pre-index treatment rates were similarly low, ranging from 9.4% (hip) to 16.6% (vertebral) among Medicare patients, and 7.5% (NHNV) to 14.4% (vertebral) in Commercial patients. Osteoporosis treatment rates improved significantly in the postfracture year, ranging from 12.5% (NHNV) to 26.5% (vertebral) among Medicare patients, and 8.3% (NHNV) to 21.4% (vertebral) in Commercial patients. Larger increases in diagnosis rates and smaller increases in treatment rates were observed in stratified analyses of men and women and of different age groups, with women and older patients having higher overall rates of diagnosis and treatment before and after fracture. In men and women, osteoporosis diagnosis rates were low before the index fracture and improved substantially after the fracture, yet still remained low overall (under 50%). Osteoporosis treatment rates among patients experiencing a fracture were low before the index fracture and improved only minimally afterwards. This study was funded by Merck & Co. Other than through the employer relationship disclosed here, Merck & Co. did not have a role in the study design, data collection, interpretation of the data, in writing of the manuscript, or in the decision to submit the manuscript for publication. Weaver is an employee of Merck & Co. Sajjan was an employee of Merck & Co. and owned stock in the company at the time of the study. Lewiecki has received consulting and/or speaker honoraria from Merck & Co., AbbVie, AgNovos Healthcare, Alexion Pharmaceuticals, Amgen, Eli Lilly and Company, Radius Health, Shire, and TheraNova, along with research grant support from Merck & Co., Amgen, and Eli Lilly and Company, and serves as a board member for the National Osteoporosis Foundation, the International Society for Clinical Densitometry, and the Osteoporosis Foundation of New Mexico. Harris has received consulting honoraria from Merck & Co., Alexion Pharmaceuticals, Amgen, Eli Lilly and Company, Gilead

  18. Real-world treatment patterns and opioid use in chronic low back pain patients initiating duloxetine versus standard of care

    Directory of Open Access Journals (Sweden)

    Andrews JS

    2013-11-01

    Full Text Available Jeffrey Scott Andrews,1 Ning Wu,2 Shih-Yin Chen,2 Xia Yu,2 Xiaomei Peng,1 Diego Novick1 1Global Health Outcomes, Eli Lilly and Company, Indianapolis, IN, USA; 2Evidera, Lexington, MA, USA Abstract: To describe the use of pain medications in patients with chronic low back pain (CLBP after initiating duloxetine or standard of care (SOC [muscle relaxants, gabapentin, pregabalin, venlafaxine, and tricyclic antidepressants] for pain management, pharmacy and medical claims from Surveillance Data, Inc (SDI Health were analyzed. Adult patients with CLBP who initiated duloxetine or SOC between November 2010 and April 2011 were identified. Treatment initiation was defined as no pill coverage for duloxetine or SOC in the previous 90 days. Included patients had no opioid use in the 90 days before initiation. Propensity score matching was used to select patients with similar baseline demographic and clinical characteristics for duloxetine and SOC cohorts. Compliance with index medication was assessed via medication possession ratio (MPR and proportion of days covered (PDC for 6 months after initiation. The proportion of patients receiving opioids and days on opioids after index date were assessed, and regression models were estimated to compare opioid use between cohorts. A total of 766 patients initiated duloxetine and 6,206 patients initiated SOC. After matching, 743 patients were selected for the duloxetine (mean age 57 years; female 74% and SOC (mean age 57 years; female 75% cohorts, respectively. Of the duloxetine cohort, 92% started on or below recommended daily dose (≤60 mg. The duloxetine cohort had significantly higher MPR (0.78 versus [vs] 0.60 and PDC (0.50 vs 0.31, were less likely to use opioids (45% vs 61%, and had fewer days on opioids (median 0 vs 7 days than the SOC cohort (all P < 0.001. After adjusting for demographic and clinical characteristics, the duloxetine cohort initiated opioids later than the SOC cohort (hazard ratio 0.77, 95

  19. Probiotics

    Directory of Open Access Journals (Sweden)

    Gupta V

    2009-01-01

    Full Text Available The term "probiotic" was first used in 1965, by Lilly and Stillwell, to describe substances secreted by one organism which stimulate the growth of another. The use of antibiotics, immunosuppressive therapy and irradiation, amongst other means of treatment, may cause alterations in the composition and have an effect on the GIT flora. Therefore, the introduction of beneficial bacterial species to GI tract may be a very attractive option to re-establish the microbial equilibrium and prevent disease. Prebiotic is a non-digestible food ingredient that confers benefits on the host by selectively stimulating one bacterium or a group of bacteria in the colon with probiotic properties. Both probiotics and prebiotics are together called as Synbiotics. Various bacterial genera most commonly used in probiotic preparations are Lactobacillus, Bifidobacterium, Escherichia, Enterococcus, Bacillus and Streptococcus . Some fungal strains belonging to Saccharomyces have also been used. Probiotics have been shown to be effective in varied clinical conditions- ranging from infantile diarrhoea, necrotizing enterocolitis, antibiotic-associated diarrhoea, relapsing Clostridium difficle colitis, Helicobacter pylori infections, inflammatory bowel disease to cancer, female uro-genital infection and surgical infections. Lactobacillus rhamnosus strain GG has proven beneficial affects on intestinal immunity. It increases the number of IgA and other immunoglobulins secreting cells in the intestinal mucosa. It also stimulates local release of interferons. It facilitates antigen transport to underlying lymphoid cells, which serves to increase antigen uptake in Peyer′s patches. Probiotics are live microorganisms, so it is possible that they may result in infection in the host. The risk and morbidity of sepsis due to probiotic bacteria should be weighed against the potential for sepsis due to more pathological bacteria and the morbidity of diseases for which probiotic bacteria

  20. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society.

    Science.gov (United States)

    Seaquist, Elizabeth R; Anderson, John; Childs, Belinda; Cryer, Philip; Dagogo-Jack, Samuel; Fish, Lisa; Heller, Simon R; Rodriguez, Henry; Rosenzweig, James; Vigersky, Robert

    2013-05-01

    To review the evidence about the impact of hypoglycemia on patients with diabetes that has become available since the past reviews of this subject by the American Diabetes Association and The Endocrine Society and to provide guidance about how this new information should be incorporated into clinical practice. Five members of the American Diabetes Association and five members of The Endocrine Society with expertise in different aspects of hypoglycemia were invited by the Chair, who is a member of both, to participate in a planning conference call and a 2-day meeting that was also attended by staff from both organizations. Subsequent communications took place via e-mail and phone calls. The writing group consisted of those invitees who participated in the writing of the manuscript. The workgroup meeting was supported by educational grants to the American Diabetes Association from Lilly USA, LLC and Novo Nordisk and sponsorship to the American Diabetes Association from Sanofi. The sponsors had no input into the development of or content of the report. The writing group considered data from recent clinical trials and other studies to update the prior workgroup report. Unpublished data were not used. Expert opinion was used to develop some conclusions. Consensus was achieved by group discussion during conference calls and face-to-face meetings, as well as by iterative revisions of the written document. The document was reviewed and approved by the American Diabetes Association's Professional Practice Committee in October 2012 and approved by the Executive Committee of the Board of Directors in November 2012 and was reviewed and approved by The Endocrine Society's Clinical Affairs Core Committee in October 2012 and by Council in November 2012. The workgroup reconfirmed the previous definitions of hypoglycemia in diabetes, reviewed the implications of hypoglycemia on both short- and long-term outcomes, considered the implications of hypoglycemia on treatment outcomes

  1. Quality rating of MR-cholangiopancreatography with oral application of iron oxide particles

    International Nuclear Information System (INIS)

    Lorenzen, M.; Wedegaertner, U.; Fiehler, J.; Adam, G.

    2003-01-01

    Purpose: To compare image quality in magnetic resonance cholangiopancreatography (MRCP) performed with and without oral application of Loesferron trademark (ferrous gluconate, Lilly Pharma, Hamburg). Materials and Methods: A prospective study compares MRCPs performed on 52 patients with a 1.5 T clinical whole body scanner using a standard body coil. After randomization, patients ingested either 0.5 l of Loeseferron trademark (n=27, group 1) or no oral contrast agent (n=25, group 2) prior to the examination. 7 RARE (40 to 20 ) sequences were obtained, followed by selected 3 mm HASTE (T 2 -weighted with fat suppression) sequences. After blinding, image quality was rated by two radiologists using a scale of 1 (not discernible) to 5 (very well discernible). The following sections of the biliary ductal system were evaluated: left and right hepatic duct, extrahepatic bile duct and intrapancreatic bile duct. The pancreatic duct was evaluated by its location: head, body and tail of the pancreas. A Wilcoxon-Mann-Whitney test was used to determine significant differences (p trademark was well tolerated by all patients, and all sequences could be acquired and evaluated in all 52 patients. For the different sections of the biliary system, the mean ratings with and without Loesferron trademark were, respectively, 3.28 and 3.36 for the left hepatic duct, 3.26 and 3.33 for the right hepatic duct, 3.46 and 4.0 for the extrahepatic bile duct, and 2.8 and 3.48 for the intrapancreatic bile duct. The corresponding ratings for the pancreatic duct were 2.8 and 3.24 for the pancreatic head, 2.84 and 3.38 for the pancreatic body, and 2.68 and 3.22 for the pancreatic tail. The differences with and without contrast agent were not statistically significant. Interobserver variability was between 0.37 for the pancreatic duct in the tail of the pancreas and 0.66 for the right hepatic duct. Conclusion: Despite the trend toward a better rating of the image quality for all sections of the

  2. The use of random-effects models to identify health care center-related characteristics modifying the effect of antipsychotic drugs

    Directory of Open Access Journals (Sweden)

    Nordon C

    2017-12-01

    Full Text Available Clementine Nordon,1 Constance Battin,1 Helene Verdoux,2 Josef Maria Haro,3 Mark Belger,4 Lucien Abenhaim,1 Tjeerd Pieter van Staa5 On behalf of the IMI GetReal WP2 Group 1Epidemiological Research, Analytica LASER, Paris, 2Population Health Research Center, Team Pharmaco-Epidemiology, UMR 1219, Bordeaux-2 University, INSERM, Bordeaux, France; 3Parc Sanitari Sant Joan de Deu, CIBERSAM, University of Barcelona, Barcelona, Spain; 4Eli Lilly and Company Limited, Erl Wood Manor, Windlesham, 5Farr Institute, University of Manchester, Manchester, UK Purpose: A case study was conducted, exploring methods to identify drugs effects modifiers, at a health care center level.Patients and methods: Data were drawn from the Schizophrenia Outpatient Health Outcome cohort, including hierarchical information on 6641 patients, recruited from 899 health care centers from across ten European countries. Center-level characteristics included the following: psychiatrist’s gender, age, length of practice experience, practice setting and type, countries’ Healthcare System Efficiency score, and psychiatrist density in the country. Mixed multivariable linear regression models were used: 1 to estimate antipsychotic drugs’ effectiveness (defined as the association between patients’ outcome at 3 months – dependent variable, continuous – and antipsychotic drug initiation at baseline – drug A vs other antipsychotic drug; 2 to estimate the similarity between clustered data (using the intra-cluster correlation coefficient; and 3 to explore antipsychotic drug effects modification by center-related characteristics (using the addition of an interaction term.Results: About 23% of the variance found for patients’ outcome was explained by unmeasured confounding at a center level. Psychiatrists’ practice experience was found to be associated with patient outcomes (p=0.04 and modified the relative effect of “drug A” (p<0.001, independent of center- or patient

  3. Treatment patterns in patients with type 2 diabetes mellitus treated with glucagon-like peptide-1 receptor agonists: Higher adherence and persistence with dulaglutide compared with once-weekly exenatide and liraglutide.

    Science.gov (United States)

    Alatorre, Carlos; Fernández Landó, Laura; Yu, Maria; Brown, Katelyn; Montejano, Leslie; Juneau, Paul; Mody, Reema; Swindle, Ralph

    2017-07-01

    To compare adherence (proportion of days covered [PDC]), persistence, and treatment patterns among patients with type 2 diabetes mellitus (T2DM) newly initiating glucagon-like peptide-1 receptor agonists (GLP-1RAs). More specifically, the main objectives were to compare dulaglutide vs exenatide once weekly and dulaglutide vs liraglutide. Patients with T2DM newly initiating dulaglutide, albiglutide, exenatide once weekly, exenatide twice daily and liraglutide between November 2014 and April 2015 were hierarchically selected from Truven Health's MarketScan Research Databases. Propensity score matching was used to account for selection bias. Adherence to and persistence with the index GLP-1RA, and switching and augmentation patterns were assessed during the 6-month post-index period. Mean adherence for the matched cohorts was significantly higher for dulaglutide than for exenatide once weekly (0.72 vs 0.61; P  < .0001) and liraglutide (0.71 vs 0.67; P  < .0001). The percentage of patients achieving PDC ≥ 0.80 was significantly higher for dulaglutide compared with exenatide once weekly (54.2% vs 37.9%; P  < .0001) and liraglutide (53.5% vs 44.3%; P  < .0001). The mean (standard deviation) days on treatment for all matched patients was significantly higher for patients in the dulaglutide cohort compared with those in the exenatide once-weekly (148.4 [55.4] vs 123.6 [61.6]; P  < .0001) and liraglutide cohorts (146.0 [56.9] vs 137.4 [60.1]; P  < .0001). A significantly lower proportion of patients on dulaglutide discontinued treatment compared with those on exenatide once weekly (26.2% vs 48.4%; P  < .0001) and those on liraglutide (28.0% vs 35.6%; P  < .0001). Dulaglutide initiators had significantly higher adherence, were more persistent, and had lower discontinuation rates compared with initiators of exenatide once weekly or liraglutide during the 6-month follow-up period. © 2017 Eli Lilly and Company. Diabetes, Obesity and

  4. Wind field near complex terrain using numerical weather prediction model

    Science.gov (United States)

    Chim, Kin-Sang

    The PennState/NCAR MM5 model was modified to simulate an idealized flow pass through a 3D obstacle in the Micro- Alpha Scale domain. The obstacle used were the idealized Gaussian obstacle and the real topography of Lantau Island of Hong Kong. The Froude number under study is ranged from 0.22 to 1.5. Regime diagrams for both the idealized Gaussian obstacle and Lantau island were constructed. This work is divided into five parts. The first part is the problem definition and the literature review of the related publications. The second part briefly discuss as the PennState/NCAR MM5 model and a case study of long- range transport is included. The third part is devoted to the modification and the verification of the PennState/NCAR MM5 model on the Micro-Alpha Scale domain. The implementation of the Orlanski (1976) open boundary condition is included with the method of single sounding initialization of the model. Moreover, an upper dissipative layer, Klemp and Lilly (1978), is implemented on the model. The simulated result is verified by the Automatic Weather Station (AWS) data and the Wind Profiler data. Four different types of Planetary Boundary Layer (PBL) parameterization schemes have been investigated in order to find out the most suitable one for Micro-Alpha Scale domain in terms of both accuracy and efficiency. Bulk Aerodynamic type of PBL parameterization scheme is found to be the most suitable PBL parameterization scheme. Investigation of the free- slip lower boundary condition is performed and the simulated result is compared with that with friction. The fourth part is the use of the modified PennState/NCAR MM5 model for an idealized flow simulation. The idealized uniform flow used is nonhydrostatic and has constant Froude number. Sensitivity test is performed by varying the Froude number and the regime diagram is constructed. Moreover, nondimensional drag is found to be useful for regime identification. The model result is also compared with the analytic

  5. DOW AGROSCIENCES TODAY AND NEW REVOLUTIONARY SOLUTIONS

    Directory of Open Access Journals (Sweden)

    Slavko Vujević

    2008-09-01

    Full Text Available Dow AgroSciences LLC, based in Indianapolis, Indiana, USA, is a top tier agricultural company providing innovative crop protection, pest and vegetation management, seed, and agricultural biotechnology solutions to serve the world's growing population. Global sales for Dow AgroSciences, a wholly owned subsidiary of The Dow Chemical Company, are $3.8 billion. The company's roots in the agricultural marketplace date back to 1950 as the agricultural unit of The Dow Chemical Company and as part of Eli Lilly and Company's agricultural business. In 1989, the DowElanco joint venture was formed, and the company continued to develop new products and acquire strategic businesses. DowElanco acquired majority ownership in Mycogen Seeds in 1996; in 1997, The Dow Chemical Company acquired 100 percent of DowElanco and the company was renamed Dow AgroSciences. Other significant acquisitions include acetochlor herbicide, Cargill Hybrid Seeds, several Brazilian seed companies and the agricultural chemicals business of Rohm and Haas. Dow AgroSciences is positioned for the future through focused implementation of its strategy which revolves around productivity, portfolio management and innovation. This focus allows the company to grow through an ambitious innovation program that maximizes the products being sold today and creates new, revolutionary solutions that will surprise customers in the future. D Dow AgroSciences is committed to sustainable chemistry and has a competitive advantage in our natural products discovery capability. We've won a prestigious award for technical innovation incorporating "green" chemistry principles into chemical design, manufacture and use. Dow AgroSciences offers a full range of seeds for corn, sunflowers, canola, cotton, soybeans and alfalfa. In addition, we have developed seeds specifically bred for nutritional quality. Dow AgroSciences uses conventional breeding techniques and tools of biotechnology to produce oils that are low in

  6. Behaviours, thoughts and perceptions around mealtime insulin usage and wastage among people with type 1 and type 2 diabetes mellitus: A cross-sectional survey study.

    Science.gov (United States)

    Van Brunt, Kate; Pedersini, Riccardo; Rooney, Jillian; Corrigan, Sheila M

    2017-04-01

    People with diabetes who use mealtime insulin (MTI) were surveyed about insulin wastage and injection habits when insufficient insulin remains in a disposable prefilled pen/cartridge to administer a full dose in a single injection. Cross-sectional, online, self-reported survey of MTI usage/wastage behaviour in 400 adults with type 1 (n=120) or type 2 (n=280) diabetes mellitus administering >20units/day of MTI via 100units/ml prefilled pens/cartridges for ⩾1month, conducted in France, Germany, Italy and UK. Participants' mean±standard deviation age was 54.5±12.2years, body mass index was 29.9±7.2kg/m 2 and duration of MTI therapy was 8.6±7.8years. They administered 3.7±5.9 injections/day with meals, using 11.3±18.0 prefilled pens/cartridges per month. Overall, 63.5% split the dose across two prefilled pens/cartridges (i.e. administered two injections to obtain a full dose), 15.0% used just what remained in their current pen (i.e. took a lower-than-prescribed dose) and 36.3% discarded prefilled pens/cartridges still containing insulin (i.e. took full dose with new pen). The latter participants discarded a mean 5.5±8.2 prefilled pens/cartridges monthly still containing insulin, each containing 8.6±8.7 units of insulin. Participants who wasted insulin considered it frustrating, time-consuming and painful to inject twice. Patients taking >20units/day MTI can find transitions between insulin pens challenging. This study highlights the need to identify ways of improving transitions between pens to make transitions easier for insulin users, which could potentially improve adherence to prescribed doses and reduce waste. Copyright © 2016 Eli Lilly and Company. Published by Elsevier B.V. All rights reserved.

  7. Predictors of duloxetine adherence and persistence in patients with fibromyalgia

    Directory of Open Access Journals (Sweden)

    Cui Z

    2012-06-01

    Full Text Available Zhanglin Cui, Yang Zhao, Diego Novick, Douglas FariesEli Lilly and Company, Indianapolis, IN, USAObjectives: Adherence to medication for the treatment of fibromyalgia (FM is predictive of lower overall health-care costs, and thus a lower burden on both patients and providers. The objectives of this study were to examine the predictors of adherence to and persistence with duloxetine therapy among commercially insured FM patients, and to identify subgroups of patients with high duloxetine persistence and adherence.Study design: This cross-sectional, retrospective study analyzed medical and pharmacy records over 1 year for patients in the US aged 18–64 years with FM who initiated (no prior 90-day use duloxetine treatment in 2008.Methods: Adherence to duloxetine was measured by medication possession ratio (MPR, with high adherence defined as MPR ≥ 0.8. Persistence was defined as the duration of therapy from the index date to the earliest of: the ending date of the last prescription, the date of the first gap of >15 days between prescriptions, or the end of the study period (12 months. Demographic and clinical predictors of adherence were examined via multiple logistic regression (MLR, and subgroups of duloxetine-persistent and -adherent patients were identified using classification and regression trees (CART.Results: Among 4660 duloxetine patients, 33% achieved high adherence. Factors associated with high adherence from MLR included older age, North Central and Northeast regions, prior venlafaxine, pregabalin, selective serotonin reuptake inhibitor (SSRI, or other antidepressant use, or comorbid dyslipidemia or osteoarthritis (all P < 0.05. CART analysis revealed that patients with prior antidepressant use, aged ≥46, or prior osteoarthritis had higher MPR (all P < 0.05, and patients aged ≥45 with a history of SSRI, venlafaxine, or anticonvulsant use had longer duration of therapy (all P < 0.05.Conclusions: Patients with high adherence to and

  8. Comparing common reasons for inpatient and outpatient visits between commercially-insured duloxetine or pregabalin initiators with fibromyalgia

    Directory of Open Access Journals (Sweden)

    Zhao Y

    2012-10-01

    Full Text Available Yang Zhao,1 Peter Sun,2 Mark Bernauer31Eli Lilly and Company, 2Kailo Research Group, 3OptumInsight, Indianapolis, IN, USABackground: The purpose of this study was to examine the main reasons for inpatient or outpatient visits after initiating duloxetine or pregabalin.Methods: Commercially insured patients with fibromyalgia and aged 18–64 years who initiated duloxetine or pregabalin in 2006 with 12-month continuous enrollment before and after initiation were identified. Duloxetine and pregabalin cohorts with similar demographics, pre-index clinical and economic characteristics, and pre-index treatment patterns were constructed via propensity scoring stratification. Reasons for inpatient admissions, physician office visits, outpatient hospital visits, emergency room visits, and primary or specialty care visits over the 12 months post-index period were examined and compared. Logistic regression was used to assess the contribution of duloxetine versus pregabalin initiation to the most common reasons for visits, controlling for cross-cohort differences.Results: Per the study design, the duloxetine (n = 3711 and pregabalin (n = 4111 cohorts had similar demographics (mean age 51 years, 83% female and health care costs over the 12-month pre-index period. Total health care costs during the 12-month post-index period were significantly lower for duloxetine patients than for pregabalin patients ($19,378 versus $27,045, P < 0.05. Eight of the 10 most common reasons for inpatient admissions and outpatient hospital (physician office, emergency room, primary or specialty care visits were the same for both groups. Controlling for cross-cohort differences, duloxetine patients were less likely to be hospitalized due to an intervertebral disc disorder or major depressive disorder, to have a physician office visit due to nonspecific backache/other back/neck pain (NB/OB/NP disorder, or to go to specialty care due to a soft tissue, NB/OP/NP, or intervertebral disc

  9. Effect of Mars Atmospheric Loss on Snow Melt Potential in a 3.5 Gyr Mars Climate Evolution Model

    Science.gov (United States)

    Mansfield, Megan; Kite, Edwin S.; Mischna, Michael A.

    2018-04-01

    Post-Noachian Martian paleochannels indicate the existence of liquid water on the surface of Mars after about 3.5 Gya (Irwin et al., 2015, https://doi.org/10.1016/j.geomorph.2014.10.012; Palucis et al., 2016, https://doi.org/10.1002/2015JE004905). In order to explore the effects of variations in CO2 partial pressure and obliquity on the possibility of surface water, we created a zero-dimensional surface energy balance model. We combine this model with physically consistent orbital histories to track conditions over the last 3.5 Gyr of Martian history. We find that melting is allowed for atmospheric pressures corresponding to exponential loss rates of dP/dt∝t-3.73 or faster, but this rate is within 0.5σ of the rate calculated from initial measurements made by the Mars Atmosphere and Volatile EvolutioN (MAVEN) mission, if we assume all the escaping oxygen measured by MAVEN comes from atmospheric CO2 (Lillis et al., 2017, https://doi.org/10.1002/2016JA023525; Tu et al., 2015, https://doi.org/10.1051/0004-6361/201526146). Melting at this loss rate matches selected key geologic constraints on the formation of Hesperian river networks, assuming optimal melt conditions during the warmest part of each Mars year (Irwin et al., 2015, https://doi.org/10.1016/j.geomorph.2014.10.012; Kite, Gao, et al., 2017, https://doi.org/10.1038/ngeo3033; Kite, Sneed et al., 2017, https://doi.org/10.1002/2017GL072660; Stopar et al., 2006, https://doi.org/10.1016/j.gca.2006.07.039). The atmospheric pressure has a larger effect on the surface energy than changes in Mars's mean obliquity. These results show that initial measurements of atmosphere loss by MAVEN are consistent with atmospheric loss being the dominant process that switched Mars from a melt-permitting to a melt-absent climate (Jakosky et al., 2017, https://doi.org/10.1126/science.aai7721), but non-CO2 warming will be required if <2 Gya paleochannels are confirmed or if most of the escaping oxygen measured by MAVEN comes from H2O.

  10. Sisseminekuks : [luuletused] / Anna Haava ; [Impressioonid]: Viiu Härm

    Index Scriptorium Estoniae

    Haava, Anna, pseud., 1864-1957

    2004-01-01

    Sisu: Sisseminekuks ; Kartus ; Ööbikule ; Käokene, kuldalindu ; Mis sa tahad, kevade? ; Ei tule uni ; Hoia ennast; Tuksuv süda ; Sina oled kelm ; Hinge hellal' igatsusel' ; Kõik kallile ; Soov ; Unes nägin ; Võin ; Sinu silmad ; Sinu silmist pilk ; Kallis, sul on kuldne süda ; Sa kõige armsam mulle ; Oh võiksin ; Lill ; Nõmmelill ; Meie Mihkel ; Koidulale ; Ehitage rahukojad ; Emakeel ; Isamaja ; Väsinud ; Oh kuhu ma lähen? ; Ööbiku surm ; Ei saa mitte vaiki olla ; Ma olen näinud ; Südameta ; Sellepärast ; See oli ilusal õiekuul; Esimese lume ajal ; Mina vaat'sin muru pääle ; Ikka kurjalt sa mind vaatad ; Oh ma isegi ei tea ; Mis on luule paljalt sõnas? ; Oh oleksin ära surnud ; Lee ääres ; Sinu nimi ; Hoia vahest aken lahti ; Jumalaga jättes vaat'sid ; Ma laulan ; Ei oma õnne peita ; Küll oli ilus mu õieke ; Oh ära sa küsi ; Ei tule luule tuulest ; Köögis seisab ; Järv leegib eha paistel ; Sinu vanaema ; Nii ta on ; Tead küll, mu kuldkallis ; Ma lähen üle nõmme ; Lenda, lepatriinuke ; Vesi voolab, vesi kohab ; Üks ainus kord ; Oh kevade, oh õie-aeg ; Suur kontsert ; Kuupaistel ; Mets kohiseb ; Lind läks magama ; Kui sa tuled, too mull' lilli ; Sinilillekesed ; Ei ole sina minu ingel ; Ei mina õnne usu ; Viimast laulu ei saa laulda ; Kõige ilusam luule ; Üks on minul püham koda! ; Sa oled suurem kui su saatus ; Mu kodumaa, kus oled sa? ; Eest ära! ; Kui kandlekeeled katkevad ; Ma kõnnin koiduvalgel ; Mu mured kõik matsin ma maha ; Kui ma sulle armas olen ; Kas tahad tulla minuga? ; Sa vaata ette, süda! ; Truus sõpruses ma tahan ; Su silmade sügavuses ; Siis mine! ; See oli siis ; Mu süda usub ; Sind teretame, kuldapäike ; Mind jumalaga jätsid ; Sääl kord kasvab kaunis kodu ; Me oleme põhjamaa lapsed ; Hilised lilled ; Sa küsid, kus mu kodu ; külm ; Sina vaikiv, sügav öö ; Ju õitsvad kõik hellerheinad ; Öösünges kohab ; Kui saaks mullegi kord kodu ; On püha mulle mu kodumaa muld ; Oma hind vaid vaba

  11. Long-acting insulins alter milk composition and metabolism of lactating dairy cows.

    Science.gov (United States)

    Winkelman, L A; Overton, T R

    2013-01-01

    This study investigated the effect of 2 different types of long-acting insulin on milk production, milk composition, and metabolism in lactating dairy cows. Multiparous cows (n=30) averaging 88 d in milk were assigned to one of 3 treatments in a completely randomized design. Treatments consisted of control (C), Humulin-N (H; Eli Lilly and Company, Indianapolis, IN), and insulin glargine (L). The H and L treatments were administered twice daily at 12-h intervals via subcutaneous injection for 10d. Cows were milked twice daily, and milk composition was determined every other day. Mammary biopsies were conducted on d 11, and mammary proteins extracted from the biopsies were analyzed by Western blot for components of insulin and mammalian target of rapamycin signaling pathways. Treatment had no effect on dry matter intake or milk yield. Treatment with both forms of long-acting insulin increased milk protein content and tended to increase milk protein yield over the 10-d treatment period. Analysis of milk N fractions from samples collected on d 10 of treatment suggested that cows administered L tended to have higher yields of milk protein fractions than cows administered H. Milk fat content and yield tended to be increased for cows administered long-acting insulins. Lactose content and yields were decreased by treatment with long-acting insulins. Administration of long-acting insulins, particularly L, tended to shift milk fatty acid composition toward increased short- and medium-chain fatty acids and decreased long-chain fatty acids. Plasma concentrations of glucose and urea N were lower for cows administered long-acting insulins; interactions of treatment and sampling time were indicative of more pronounced effects of L than H on these metabolites. Concentrations of nonesterified fatty acids and insulin were increased in cows administered long-acting insulins. Decreased concentrations of urea N in both plasma and milk suggested more efficient use of N in cows

  12. Large-Eddy Simulations of Flows in Complex Terrain

    Science.gov (United States)

    Kosovic, B.; Lundquist, K. A.

    2011-12-01

    Large-eddy simulation as a methodology for numerical simulation of turbulent flows was first developed to study turbulent flows in atmospheric by Lilly (1967). The first LES were carried by Deardorff (1970) who used these simulations to study atmospheric boundary layers. Ever since, LES has been extensively used to study canonical atmospheric boundary layers, in most cases flat plate boundary layers under the assumption of horizontal homogeneity. Carefully designed LES of canonical convective and neutrally stratified and more recently stably stratified atmospheric boundary layers have contributed significantly to development of better understanding of these flows and their parameterizations in large scale models. These simulations were often carried out using codes specifically designed and developed for large-eddy simulations of horizontally homogeneous flows with periodic lateral boundary conditions. Recent developments in multi-scale numerical simulations of atmospheric flows enable numerical weather prediction (NWP) codes such as ARPS (Chow and Street, 2009), COAMPS (Golaz et al., 2009) and Weather Research and Forecasting model, to be used nearly seamlessly across a wide range of atmospheric scales from synoptic down to turbulent scales in atmospheric boundary layers. Before we can with confidence carry out multi-scale simulations of atmospheric flows, NWP codes must be validated for accurate performance in simulating flows over complex or inhomogeneous terrain. We therefore carry out validation of WRF-LES for simulations of flows over complex terrain using data from Askervein Hill (Taylor and Teunissen, 1985, 1987) and METCRAX (Whiteman et al., 2008) field experiments. WRF's nesting capability is employed with a one-way nested inner domain that includes complex terrain representation while the coarser outer nest is used to spin up fully developed atmospheric boundary layer turbulence and thus represent accurately inflow to the inner domain. LES of a

  13. Using GRIDVIEW to Better Understand the Early Bombardment History of the Moon, Mars and Earth

    Science.gov (United States)

    Frey, Herbert

    2012-01-01

    For more than a decade we have used GRIDVIEW to help analyze topographic and related data for Mars and more recently for the Moon. Our focus has been to employ the stretching, contouring, profiling, circle-fitting and other capabilities of GRIDVIEW to search for Quasi-Circular Depressions (CTAs) in MOLA, LOLA and other topographic data, and for Circular Thin Areas (CTAs) in Mars and Moon model crustal thickness data. Both QCDs and CTAs likely represent buried or obscured impact craters not readily visible in image data. We found clear evidence for a much larger population of buried impact craters in the northern lowlands of Mars (Frey et al. 2002), suggesting that part of the Red Planet is not significantly younger than the southern highlands. Edgar and Frey (2008) found that the N(300) crater retention ages of both areas were essentially identical, a conclusion confirmed by Wyatt (unpublished data) using more recent crustal thickness data for Mars. MOLA topographic data and MOLA-derived crustal thickness data were used to both identify a large number of previously unrecognized very large impact basins (D> 1000 km) on Mars and to determine relative crater retention ages for them (Frey, 2008). The distribution of N(300) CRAs suggested most formed in a relatively short interval of time. This dating also suggested the main magnetic field of Mars disappeared during this period (Lillis et al., 2008), because only the youngest basins systematically lack a remagnetized signature. Similar QCD and CTA analysis of first Clementine (Frey, 2011) and more recently LOLA topographic and LOLA-derived crustal thickness data for the Moon (Frey et al., 2011) revealed a significantly larger population of impact basins > 300 km in diameter than previously known. N(50) CRAs suggest a two-peak distribution of ages (Frey, 2012). An improved counting process confirms the two peaks, perhaps indicating both a pre-Nectaris Early Heavy Bombardment (EHB) as well as a Late Heavy Bombardment (LHB

  14. The noradrenergic paradox: implications in the management of depression and anxiety

    Directory of Open Access Journals (Sweden)

    Montoya A

    2016-03-01

    Full Text Available Alonso Montoya,1 Robert Bruins,1 Martin A Katzman,2 Pierre Blier3 1Eli Lilly Canada Inc, 2START Clinic for the Mood and Anxiety Disorders, Toronto, 3Mood Disorders Research Unit, Institute of Mental Health Research, University of Ottawa, Ottawa, ON, Canada Abstract: Both major depressive disorder and the anxiety disorders are major causes of ­disability and markedly contribute to a significant global burden of the disease worldwide. In part because of the significant socioeconomic burden associated with these disorders, theories have been developed to specifically build clinical treatment approaches. One such theory, the monoaminergic hypothesis, has led to the development of several generations of selective and nonselective inhibitors of transporters of serotonin and norepinephrine, with the goal of augmenting monoaminergic transmission. These efforts have led to considerable success in the development of antidepressant therapeutics. However, there is a strong correlation between enhanced noradrenergic activity and fear and anxiety. Consequently, some physicians have expressed concerns that the same enhanced noradrenergic activity that alleviates depression could also promote anxiety. The fact that the serotonergic and noradrenergic reuptake inhibitors are successfully used in the treatment of anxiety and panic disorders seems paradoxical. This review was undertaken to determine if any clinical evidence exists to show that serotonergic and noradrenergic reuptake inhibitors can cause anxiety. The PubMed, EMBASE, and Cochrane Library databases were searched, and the results limited to randomized, double-blind, placebo-controlled studies performed in nongeriatric adults and with clear outcome measures were reported. Based on these criteria, a total of 52 studies were examined. Patients in these studies suffered from depression or anxiety disorders (generalized and social anxiety disorders, panic disorder, and posttraumatic stress disorder. The

  15. Safety and effectiveness of rapid-acting intramuscular olanzapine for agitation associated with schizophrenia – Japan postmarketing surveillance study

    Directory of Open Access Journals (Sweden)

    Katagiri H

    2018-01-01

    Full Text Available Hideaki Katagiri,1 Masanori Taketsuna,2 Shinpei Kondo,3 Kenta Kajimoto,4 Etsuko Aoi,5 Yuka Tanji1 1Bio Medicine, 2Statistical Sciences, 3Post Marketing Study Management, 4Scientific Communications, Medicines Development Unit Japan, 5Global Patient Safety Japan, Quality and Patient Safety, Eli Lilly Japan K.K., Kobe, Japan Objective: The objective of this study was to evaluate the safety and effectiveness of rapid-acting intramuscular (IM olanzapine in the treatment of acute agitation associated with schizophrenia in real-world clinical settings in Japan.Methods: In this multicenter, postmarketing surveillance (PMS study, patients with acute agitation associated with schizophrenia were treated with IM olanzapine daily in a daily clinical setting. The observational period ranged from 1 to 7 days, including the day of initial administration. Safety was assessed by reporting treatment-emergent adverse events (TEAEs and adverse drug reactions (ADRs. The Positive and Negative Syndrome Scale – Excited Component (PANSS-EC score was used to evaluate effectiveness at baseline and at 2 hours (after each administration, 2 days, and 3 days (end of the observational period from the last administration of the IM olanzapine injection.Results: The safety analysis set included 999 patients, and the initial dose of 10 mg was administered to 955 patients. TEAEs were reported in 28 patients (36 events, the most common of which were dyslalia (5 patients, akathisia and somno­lence (4 patients each, hepatic function abnormal (3 patients, and constipation and dehydration (2 patients each. One serious adverse event of akathisia occurred during the observation period. The PANSS-EC score (mean ± standard deviation was 23.3±6.4 (n=625 at baseline, 16.9±7.0 (n=522 at 2 hours after initial injection, and 14.9±6.5 (n=650 at the last observation carried forward.Conclusion: The results of this Japanese PMS study demonstrated that IM olanzapine is safe and has a

  16. AMCP Partnership Forum: Driving Value and Outcomes in Oncology.

    Science.gov (United States)

    2017-05-01

    arrangements. Addressing these challenges could lead to improving cancer treatment. The AMCP Partnership Forum titled "Driving Value and Outcomes in Oncology" and the development of this report were supported by AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Foundation Medicine, IntrinsiQ Specialty Solutions, Janssen Oncology and Johnson and Johnson Health Systems, Eli Lilly and Company, National Pharmaceutical Council, Novartis Pharmaceuticals Corporation, Pharmaceutical Research and Manufacturers of America, Sanofi, Takeda Oncology, and Xcenda.

  17. Ease of use and patient preference injection simulation study comparing two prefilled insulin pens.

    Science.gov (United States)

    Clark, Paula E; Valentine, Virginia; Bodie, Jennifer N; Sarwat, Samiha

    2010-07-01

    To determine patient ease of use and preference for the Humalog KwikPen* (prefilled insulin lispro [Humalog dagger] pen, Eli Lilly and Company, Indianapolis, IN, USA) (insulin lispro pen) versus the Next Generation FlexPen double dagger (prefilled insulin aspart [NovoRapid section sign ] pen, Novo Nordisk A/S, Bagsvaerd, Denmark) (insulin aspart pen). This was a randomized, open-label, 2-period, 8-sequence crossover study in insulin pen-naïve patients with diabetes. Randomized patients (N = 367) received device training, then simulated low- (15 U) and high- (60 U) dose insulin injections with an appliance. Patients rated pens using an ease of use questionnaire and were asked separately for final pen preferences. The Insulin Device 'Ease of Use' Battery is a 10-item questionnaire with a 7-point scale (higher scores reflect greater ease of use). The primary objective was to determine pen preference for 'easy to press to inject my dose' (by comparing composite scores [low- plus high-dose]). Secondary objectives were to determine pen preference on select questionnaire items (from composite scores), final pen preference, and summary responses for all questionnaire items. On the primary endpoint, 'easy to press to inject my dose,' a statistically significant majority of patients with a preference chose the insulin lispro pen over the insulin aspart pen (68.4%, 95% CI = 62.7-73.6%). Statistically significant majorities of patients with a preference also favored the insulin lispro pen on secondary items: 'easy to hold in my hand when I inject' (64.9%, 95% CI = 58.8-70.7%), 'easy to use when I am in a public place' (67.5%, 95% CI = 61.0-73.6%), and 'overall easy to use' (69.9%, 95% CI = 63.9-75.4%). A statistically significant majority of patients had a final preference for the insulin lispro pen (67.3%, 95% CI = 62.2-72.1%). Among pen-naïve patients with diabetes who had a preference, the majority preferred the insulin lispro pen over the insulin aspart pen with regard

  18. Preference for pharmaceutical formulation and treatment process attributes

    Directory of Open Access Journals (Sweden)

    Stewart KD

    2016-07-01

    Full Text Available Katie D Stewart,1 Joseph A Johnston,2 Louis S Matza,1 Sarah E Curtis,2 Henry A Havel,3 Stephanie A Sweetana,3 Heather L Gelhorn1 1Outcomes Research, Evidera, Bethesda, MD, USA; 2Global Patient Outcomes & Real World Evidence, 3Small Molecule Design and Development, Eli Lilly & Company, Indianapolis, IN, USA Purpose: Pharmaceutical formulation and treatment process attributes, such as dose frequency and route of administration, can have an impact on quality of life, treatment adherence, and disease outcomes. The aim of this literature review was to examine studies on preferences for pharmaceutical treatment process attributes, focusing on research in diabetes, oncology, osteoporosis, and autoimmune disorders.Methods: The literature search focused on identifying studies reporting preferences for attributes of the pharmaceutical treatment process. Studies were required to use formal quantitative preference assessment methods, such as utility valuation, conjoint analysis, or contingent valuation. Searches were conducted using Medline, EMBASE, Cochrane Library, Health Economic Evaluation Database, and National Health Service Economic Evaluation Database (January 1993–October 2013.Results: A total of 42 studies met inclusion criteria: 19 diabetes, nine oncology, five osteoporosis, and nine autoimmune. Across these conditions, treatments associated with shorter treatment duration, less frequent administration, greater flexibility, and less invasive routes of administration were preferred over more burdensome or complex treatments. While efficacy and safety often had greater relative importance than treatment process, treatment process also had a quantifiable impact on preference. In some instances, particularly in diabetes and autoimmune disorders, treatment process attributes had greater relative importance than some or all efficacy and safety attributes. Some studies suggested that relative importance of treatment process depends on disease (eg

  19. Differential diagnosis of neurodegenerative dementias with nuclear medicine methods

    International Nuclear Information System (INIS)

    Kluge, R.

    2015-01-01

    Full text: Neurodegenerative dementias (NDD) are characterized by insidious onset and gradual progression of cognitive dysfunction, initially relatively focal with respect to cognitive domains and brain regions involved. Nuclear medicine techniques help to clarify differential diagnoses of syndromes such as Alzheimer’s disease (AD), dementia with Lewy bodies (DlB), posterior cortical atrophy (PCA), logopenic primary progressive aphasia (PPA), agrammatic PPA, semantic dementia (SD), behavioral variant frontotemporal dementia (bvFTD) and progressive supranuclear palsy syndrome (PSPS). The process of pathologic changes in the brain may start decades before first clinical symptoms become evident. An early diagnosis already in the pre-clinical phase of the diseases will be of immense importance when expected effective therapeutic options have been introduced. NDDs are histopathologically characterized by accumulation of pathological proteins in the brain like beta amyloid or protein tau. While radiotracers for labeling of protein tau are in preclinical evaluation, different radiotracers labeling amyloid plaques ([11C]PIB, [18F]Florbetapir (Amyvid, Fa. EliLilly), [18F]Florbetaben (Neuraceq, Fa. Piramal), [18F]Flutemetamol (vVzamyl, Fa. Ge) have already been established in clinical use during the last years. In AD these tracers are intensively accumulated in the whole cortical brain. Even an early disease can be excluded in case of a negative amyloid PET. The method is, however, not highly specific since amyloid plaques may also be present in DlB (70 – 80%), FTD (30%) orlogopenicPPA (100%). Neuronal dysfunction goes along with decreased glucose consumption. Different diseases are characterized by different topographical zones of reduced [18F]FDG uptake. In AD the posterior cingular, temporopariatal and (later) frontal cortex are affected, in DlB the pattern is similar, including the occipital cortex, in FTD the frontal cortex is affected, in nonfluent PPA the

  20. What can we learn about Mars from satellite magnetic field measurements?

    Science.gov (United States)

    Morschhauser, A.; Mittelholz, A.; Thomas, P.; Vervelidou, F.; Grott, M.; Johnson, C.; Lesur, V.; Lillis, R. J.

    2017-12-01

    The Mars orbiters MGS and MAVEN provide vector magnetic field data for Mars at a variety of altitudes, locations, and local times. In spite of the abundance of data, there are many open questions concerning the crustal magnetic field of Mars. In this contribution, we present our efforts to estimate the shutdown time of the Martian core dynamo and to estimate Martian paleopole locations, using magnetic field satellite data and models derived from these data [1]. Models are primarily based on MGS data, and we shortly present our recent advances to include MAVEN data. There exists some controversy concerning the timing of the Martian core dynamo shutdown [e.g., 2-5]. We address this question by studying the so-called visible magnetization [6-7] of impact craters larger than 400 km in diameter, and conclude that the dynamo ceased to operate in the Noachian period [8]. Further, paleopole locations have been used to constrain the dynamics of the Martian core dynamo [e.g. 4-5, 9]. However, such estimates are limited by the inherent non-uniqueness of inferring magnetization from magnetic field measurements. Here, we discuss how estimated paleopoles are influenced by this non-uniqueness and the limited signal-to-noise ratio of satellite measurements [6]. Furthermore, we discuss how paleopole locations may still be obtained from satellite magnetic field measurements. In this context, we present some new paleopole estimates for Mars including estimates of uncertainties. References: [1] A. Morschhauser et al. (2014), JGR, doi: 10.1002/2013JE004555 [2] R.J. Lillis et al. (2015), JGR, doi: 10.1002/2014je004774 [3] L.L. Hood et al. (2010), Icarus, doi: 10.1016/j.icarus.2010.01.009 [4] C. Milbury et al. (2012), JGR, doi: 10.1029/2012JE004099 [5] B. Langlais and M. Purucker (2007), PSS, 10.1016/j.pss.2006.03.008 [6] F. Vervelidou et al., On the accuracy of paleopole estimations from magnetic field measurements, GJI, under revision 2017 [7] D. Gubbins et al. (2011), GJI, doi: 10

  1. Do different clinical evidence bases lead to discordant health-technology assessment decisions? An in-depth case series across three jurisdictions

    Directory of Open Access Journals (Sweden)

    Spinner DS

    2013-01-01

    Full Text Available Daryl S Spinner,1 Julie Birt,2 Jeffrey W Walter,1 Lee Bowman,2 Josephine Mauskopf,1 Michael F Drummond,3 Catherine Copley-Merriman11RTI Health Solutions, Research Triangle Park, NC, USA; 2Eli Lilly and Company, Indianapolis, IN, United States; 3University of York, York, UKBackground: Health-technology assessment (HTA plays an important role in informing drug-reimbursement decision-making in many countries. HTA processes for the Pharmaceutical Benefits Advisory Committee (PBAC in Australia, the Common Drug Review (CDR in Canada, and the National Institute for Health and Clinical Excellence (NICE in England and Wales are among the most established in the world. In this study, we performed nine in-depth case studies to assess whether different clinical evidence bases may have influenced listing recommendations made by PBAC, CDR, and NICE.Methods: Nine drugs were selected for which the three agencies had provided listing recommendations for the same indication between 2007 and 2010. We reviewed the evidence considered for each listing recommendation, identified the similarities and differences among the clinical evidence bases considered, and evaluated the extent to which different clinical evidence bases could have contributed to different decisions based on HTA body comments and public assessment of the evidence.Results: HTA agencies reached the same recommendation for reimbursement (recommended for listing for four drugs and different recommendations for five drugs. In all cases, each agency used different evidence bases in their recommendations. The agencies considered overlapping sets of clinical comparators and trials when evaluating the same drug. While PBAC and NICE considered indirect and/or mixed-treatment comparisons, CDR did not. In some cases, CDR and/or NICE excluded trials from review if the drug and/or the comparator were not administered according to the relevant marketing authorization.Conclusions: In the listing recommendations

  2. Treatment progression in sulfonylurea and dipeptidyl peptidase-4-inhibitor cohorts of type 2 diabetes patients on metformin

    Directory of Open Access Journals (Sweden)

    Peng X

    2016-08-01

    Full Text Available Xiaomei Peng, Dingfeng Jiang, Dongju Liu, Oralee J Varnado, Jay P Bae Eli Lilly and Company, Global Patient Outcomes and Real World Evidence, Indianapolis, IN, USA Background: Metformin is an oral antidiabetic drug (OAD widely used as first-line therapy in type 2 diabetes (T2D treatments. Numerous treatment pathways after metformin failure exist. It is important to understand how treatment choices influence subsequent therapy progressions. This retrospective study compares adherence to, persistence with, and treatment progression in sulfonylurea (SU and dipeptidyl peptidase-4 (DPP-4 inhibitor patient cohorts with T2D on metformin. Methods: Using health insurance claims data, matched patient cohorts were created and OAD use was compared in patients with T2D initiating SU or DPP-4 inhibitors (index drugs since January 1, 2010, to December 31, 2010, with background metformin therapy. Propensity score matching adjusted for possible selection bias. Persistence was measured via Cox regression as days to a ≥60-day gap in index drug possession; adherence was defined as proportion of days covered (PDC ≥80%. Evolving treatment patterns were traced at 6-month intervals for 24 months following index drug discontinuation. Results: From among 19,621 and 7,484 patients in the SU and DPP-4 inhibitor cohorts, respectively, 6,758 patient pairs were matched. Persistence at 12 months in the SU cohort was 48.0% compared to 52.5% for the DPP-4 inhibitor cohort. PDC adherence (mean [SD] during the 12-month follow-up period was 63.3 (29.7 for the SU cohort and 65.5 (28.7 for the DPP-4 inhibitor cohort. PDC ≥80% was 40.5% and 43.4% in the SU and DPP-4 inhibitor cohorts, respectively. A higher percentage of patients in the SU cohort remained untreated. Following index drug discontinuation, monotherapy was more common in the SU cohort, while use of two or three OADs was more common in the DPP-4 inhibitor cohort. Insulin therapy initiation was higher in the SU

  3. A novel derivative of doxorubicin, AD198, inhibits canine transitional cell carcinoma and osteosarcoma cells in vitro.

    Science.gov (United States)

    Rathore, Kusum; Cekanova, Maria

    2015-01-01

    Doxorubicin (DOX) is one of the most commonly used chemotherapeutic treatments for a wide range of cancers. N-benzyladriamycin-14-valerate (AD198) is a lipophilic anthracycline that has been shown to target conventional and novel isoforms of protein kinase C (PKC) in cytoplasm of cells. Because of the adverse effects of DOX, including hair loss, nausea, vomiting, liver dysfunction, and cardiotoxicity, novel derivatives of DOX have been synthesized and validated. In this study, we evaluated the effects of DOX and its derivative, AD198, on cell viability of three canine transitional cell carcinoma (K9TCC) (K9TCC#1-Lillie, K9TCC#2-Dakota, K9TCC#4-Molly) and three canine osteosarcoma (K9OSA) (K9OSA#1-Zoe, K9OSA#2-Nashville, K9OSA#3-JJ) primary cancer cell lines. DOX and AD198 significantly inhibited cell proliferation in all tested K9TCC and K9OSA cell lines in a dose-dependent manner. AD198 inhibited cell viability of tested K9TCC and K9OSA cell lines more efficiently as compared to DOX at the same concentration using MTS (3-(4,5-dimethyl-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2h-tetrazolium) assay. AD198 had lower IC50 values as compared to DOX for all tested K9TCC and K9OSA cell lines. In addition, AD198 increased apoptosis in all tested K9TCC and K9OSA cell lines. AD198 increased the caspase activity in tested K9TCC and K9OSA cell lines, which was confirmed by caspase-3/7 assay, and cleavage of poly (ADP-ribose) polymerase (PARP) was confirmed by Western blotting analysis. In addition, AD198 cleaved PKC-δ, which subsequently activated the p38 signaling pathway, resulting in the apoptosis of tested K9TCC and K9OSA cell lines. Inhibition of the p38 signaling pathway by SB203580 rescued DOX- and AD198-induced apoptosis in tested K9TCC and K9OSA cell lines. Our in vitro results suggest that AD198 might be considered as a new treatment option for K9TCC and K9OSA cell lines cancers in vivo.

  4. A novel derivative of doxorubicin, AD198, inhibits canine transitional cell carcinoma and osteosarcoma cells in vitro

    Directory of Open Access Journals (Sweden)

    Rathore K

    2015-09-01

    Full Text Available Kusum Rathore, Maria Cekanova Department of Small Animal Clinical Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN, USA Abstract: Doxorubicin (DOX is one of the most commonly used chemotherapeutic treatments for a wide range of cancers. N-benzyladriamycin-14-valerate (AD198 is a lipophilic anthracycline that has been shown to target conventional and novel isoforms of protein kinase C (PKC in cytoplasm of cells. Because of the adverse effects of DOX, including hair loss, nausea, vomiting, liver dysfunction, and cardiotoxicity, novel derivatives of DOX have been synthesized and validated. In this study, we evaluated the effects of DOX and its derivative, AD198, on cell viability of three canine transitional cell carcinoma (K9TCC (K9TCC#1-Lillie, K9TCC#2-Dakota, K9TCC#4-Molly and three canine osteosarcoma (K9OSA (K9OSA#1-Zoe, K9OSA#2-Nashville, K9OSA#3-JJ primary cancer cell lines. DOX and AD198 significantly inhibited cell proliferation in all tested K9TCC and K9OSA cell lines in a dose-dependent manner. AD198 inhibited cell viability of tested K9TCC and K9OSA cell lines more efficiently as compared to DOX at the same concentration using MTS (3-(4,5-dimethyl-2-yl-5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl-2h-tetrazolium assay. AD198 had lower IC50 values as compared to DOX for all tested K9TCC and K9OSA cell lines. In addition, AD198 increased apoptosis in all tested K9TCC and K9OSA cell lines. AD198 increased the caspase activity in tested K9TCC and K9OSA cell lines, which was confirmed by caspase-3/7 assay, and cleavage of poly (ADP-ribose polymerase (PARP was confirmed by Western blotting analysis. In addition, AD198 cleaved PKC-δ, which subsequently activated the p38 signaling pathway, resulting in the apoptosis of tested K9TCC and K9OSA cell lines. Inhibition of the p38 signaling pathway by SB203580 rescued DOX- and AD198-induced apoptosis in tested K9TCC and K9OSA cell lines. Our in vitro results suggest

  5. Perceptions and impact of bipolar disorder in Japan: results of an Internet survey

    Directory of Open Access Journals (Sweden)

    Watanabe K

    2016-11-01

    Full Text Available Koichiro Watanabe,1 Eiji Harada,2 Takeshi Inoue,3 Yuka Tanji,2 Toshiaki Kikuchi1 1Department of Neuropsychiatry, Kyorin University, School of Medicine, Tokyo, 2Medical Science, Medicines Development Unit-Japan, Eli Lilly Japan KK, Hyogo, 3Department of Psychiatry, Tokyo Medical University, Tokyo, Japan Abstract: Bipolar disorder is a recurrent and episodic illness. This survey study assessed experiences and identified clinical insights of individuals with bipolar disorder. An Internet-based monitor system database was screened for patients with bipolar disorder in Japan (February and March 2013. Of 1,050 patients, 457 completed surveys, and results were analyzed with descriptive statistics. Approximately one-fourth of respondents were diagnosed with bipolar disorder on their first visit to medical institutions, although the most common initial diagnosis was depression/depressive state (65%. Mean time lag between first-time visit to a medical institution and receipt of correct diagnosis of bipolar disorder was 4 years; one-third of patients experienced more than 5 years of lag time. Three perceived reasons for lapsed time before correct diagnosis were “(patients Did not consider manic symptoms as illness, and did not tell the doctor about them,” “I (patient did not know of bipolar disorder,” and “Lack of communication between my doctor and myself (patient.” Among participants who believed that they were initially incorrectly diagnosed and improperly treated, most experienced socioeconomic problems, such as having long-term inability to work or to study (65%. Sources of encouragement for participants included “To have someone to consult with” (41% followed by having “People around me treat me the same as before” (40%. Individuals with bipolar disorder reported a time lag of many years before accurate diagnosis, and substantial burden imposed by the illness. Encouragement should be provided for individuals to live positively

  6. The Direct Cost of Managing a Rare Disease: Assessing Medical and Pharmacy Costs Associated with Duchenne Muscular Dystrophy in the United States.

    Science.gov (United States)

    Thayer, Sarah; Bell, Christopher; McDonald, Craig M

    2017-06-01

    A Duchenne muscular dystrophy (DMD) cohort was identified using a claims-based algorithm to estimate health care utilization and costs for commercially insured DMD patients in the United States. Previous analyses have used broad diagnosis codes that include a range of muscular dystrophy types as a proxy to estimate the burden of DMD. To estimate DMD-associated resource utilization and costs in a sample of patients identified via a claims-based algorithm using diagnosis codes, pharmacy prescriptions, and procedure codes unique to DMD management based on DMD clinical milestones. DMD patients were selected from a commercially insured claims database (2000-2009). Patients with claims suggestive of a non-DMD diagnosis or who were aged 30 years or older were excluded. Each DMD patient was matched by age, gender, and region to controls without DMD in a 1:10 ratio (DMD patients n = 75; controls n = 750). All-cause health care resource utilization, including emergency department, inpatient, outpatient, and physician office visits, and all-cause health care costs were examined over a minimum 1-year period. Costs were computed as total health-plan and patient-paid amounts of adjudicated medical claims (in annualized U.S. dollars). The average age of the DMD cohort was 13 years. Patients in the DMD cohort had a 10-fold increase in health care costs compared with controls ($23,005 vs. $2,277, P McDonald has been a consultant for GSK, Sarepta, PTC Therapeutics, Biomarin, and Catabasis on clinical trials regarding Duchenne muscular dystrophy clinical trial design, endpoint selection, and data analysis; Mitobridge for drug development; and Eli Lilly as part of a steering committee for clinical trials. Study concept and design were contributed primarily by Bell, along with Thayer and McDonald. Thayer collected the data, and data interpretation was performed by Thayer and Bell, along with McDonald. The manuscript was written by Thayer and Bell, along with McDonald, and revised by

  7. A comprehensive review of nongenetic prognostic and predictive factors influencing the heterogeneity of outcomes in advanced non-small-cell lung cancer

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    Cuyún Carter G

    2014-10-01

    Full Text Available Gebra Cuyún Carter,1 Amy M Barrett,2 James A Kaye,3 Astra M Liepa,1 Katherine B Winfree,1 William J John1 1Eli Lilly and Company, Indianapolis, IN, USA; 2RTI Health Solutions, Research Triangle Park, NC, USA; 3RTI Health Solutions, Waltham, MA, USA Abstract: While there have been advances in treatment options for those with advanced non-small-cell lung cancer, unmet medical needs remain, partly due to the heterogeneity of treatment effect observed among patients. The goals of this literature review were to provide updated information to complement past reviews and to identify a comprehensive set of nongenetic prognostic and predictive baseline factors that may account for heterogeneity of outcomes in advanced non-small-cell lung cancer. A review of the literature between 2000 and 2010 was performed using PubMed, Embase, and Cochrane Library. All relevant studies that met the inclusion criteria were selected and data elements were abstracted. A classification system was developed to evaluate the level of evidence for each study. A total of 54 studies were selected for inclusion. Patient-related factors (eg, performance status, sex, and age were the most extensively researched nongenetic prognostic factors, followed by disease stage and histology. Moderately researched prognostic factors were weight-related variables and number or site of metastases, and the least studied were comorbidities, previous therapy, smoking status, hemoglobin level, and health-related quality of life/symptom severity. The prognostic factors with the most consistently demonstrated associations with outcomes were performance status, number or site of metastases, previous therapy, smoking status, and health-related quality of life. Of the small number of studies that assessed predictive factors, those that were found to be significantly predictive of outcomes were performance status, age, disease stage, previous therapy, race, smoking status, sex, and histology. These

  8. Modeling of Marine Natural Hazards in the Lesser Antilles

    Science.gov (United States)

    Zahibo, Narcisse; Nikolkina, Irina; Pelinovsky, Efim

    2010-05-01

    The Caribbean Sea countries are often affected by various marine natural hazards: hurricanes and cyclones, tsunamis and flooding. The historical data of marine natural hazards for the Lesser Antilles and specially, for Guadeloupe are presented briefly. Numerical simulation of several historical tsunamis in the Caribbean Sea (1755 Lisbon trans-Atlantic tsunami, 1867 Virgin Island earthquake tsunami, 2003 Montserrat volcano tsunami) are performed within the framework of the nonlinear-shallow theory. Numerical results demonstrate the importance of the real bathymetry variability with respect to the direction of propagation of tsunami wave and its characteristics. The prognostic tsunami wave height distribution along the Caribbean Coast is computed using various forms of seismic and hydrodynamics sources. These results are used to estimate the far-field potential for tsunami hazards at coastal locations in the Caribbean Sea. The nonlinear shallow-water theory is also applied to model storm surges induced by tropical cyclones, in particular, cyclones "Lilli" in 2002 and "Dean" in 2007. Obtained results are compared with observed data. The numerical models have been tested against known analytical solutions of the nonlinear shallow-water wave equations. Obtained results are described in details in [1-7]. References [1] N. Zahibo and E. Pelinovsky, Natural Hazards and Earth System Sciences, 1, 221 (2001). [2] N. Zahibo, E. Pelinovsky, A. Yalciner, A. Kurkin, A. Koselkov and A. Zaitsev, Oceanologica Acta, 26, 609 (2003). [3] N. Zahibo, E. Pelinovsky, A. Kurkin and A. Kozelkov, Science Tsunami Hazards. 21, 202 (2003). [4] E. Pelinovsky, N. Zahibo, P. Dunkley, M. Edmonds, R. Herd, T. Talipova, A. Kozelkov and I. Nikolkina, Science of Tsunami Hazards, 22, 44 (2004). [5] N. Zahibo, E. Pelinovsky, E. Okal, A. Yalciner, C. Kharif, T. Talipova and A. Kozelkov, Science of Tsunami Hazards, 23, 25 (2005). [6] N. Zahibo, E. Pelinovsky, T. Talipova, A. Rabinovich, A. Kurkin and I

  9. On the role of the stratosphere in the process of overflow of mesoscale mountains

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    K. B. Moiseenko

    2005-12-01

    Full Text Available A 2-D, two- and three-layer stratified airflow over a mountain of arbitrary shape is considered on the assumptions that upstream wind velocity and static stability within each layer are constant (Long's model. The stratosphere is simulated by an infinitely deep upper layer with enhanced static stability.

    The analytical solution for the stream function, as well as first (linear and second order approximations to the wave drag, are obtained in hydrostatic limit N1L/U0→∞, where N1 is the Brunt-Väsälä frequency in the troposphere, L is a characteristic length of the obstacle, and U0 is upstream velocity. The results of numerical computations show the principal role of long waves in the process of interaction between the model layers for a typical mesoscale mountains for which the hydrostatic approximation proves valid in a wide range of flow parameters, in accordance with the earlier conclusions of Klemp and Lilly (1975. Partial reflection of wave energy from the tropopause produces strong influence on the value of wave drag for typical middle and upper tropospheric lapse rates, leading to a quasi-periodic dependance of wave drag on a reduced frequency $k{=}N_1{tilde H}/pi U_0$ (${tilde H}$ is tropopause height in the troposphere. The flow seems to be statically unstable for k≥2 for sufficiently large obstacles (whose height exceeds 1 km. In this case, vast regions of rotor motions and strong turbulence are predicted from model calculations in the middle troposphere and the lower stratosphere. The model calculations also point to a testify

  10. Cyclooxygenase inhibitors potentiate receptor tyrosine kinase therapies in bladder cancer cells in vitro

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    Bourn J

    2018-06-01

    -Kit receptors. RTKIs increased the expression of COX-2 in h-5637 and K9TCC#1Lillie cells. Co-treatment of indomethacin inhibited AB1010-induced COX-2 expression leading to an additive effect in inhibition of cell viability and PGE2 production in tested TCC cells.Conclusion: Co-treatment of RTKIs with indomethacin inhibited cell viability and AB1010-induced COX-2 expression resulting in decreased PGE2 production in tested TCC cells. Thus, COX inhibition may further potentiate RTKIs therapies in bladder cancer. Keywords: transitional cell carcinoma, axitinib, masitinib, cyclooxygenase-2, prostaglandin E2, indomethacin 

  11. "Alguses oli tema üksinda, sest oli küll..." : [luuletused] / Kabir ; tlk. Doris Kareva

    Index Scriptorium Estoniae

    Kabir

    2006-01-01

    Sisu: "Alguses oli tema üksinda, sest oli küll..." ; "Kõik loodud on Kõiksuse poolt..." ; "Otsid Sa mind?..." ; "Kabir oma meele puhtaks..." ; "Pole pühades järvedes midagi muud peale vee..." ; "Otsisin kelme ja kõveraid..." ; "Ütle, vend, mida küll teha..." ; "Mis kurja on teinud su juuksed..." ; "Ära tõuse, et minna õue vaatama lilli..." ; "Sinu sünd inimesena on küps vili..." ; "Öö saatsid sa magades mööda..." ; "Pole ma hindu..." ; "Ma vaatan sind..." ; "Veskikivisid vaadeldes ; "Nähes aednikku lähenemas, õhkasid pungad..." ; "Tasa, tasa tõtta, mu meel..." ; "Ära kurvasta..." ; "Imetlusväärne on teemant..." ; "Kuula, sõber, see keha on Tema lüüra..." ; "Nagu seemnes varjul on õli..." ; "Olgugi ookean leekides..." ; "Tilka, mis lahustub meres..." ; "Jõgi ja lained on üks..." ; "Kes sa oled ja kust oled tulnud?..." ; "Kaovad kuningad, kauneimad kuningannad..." ; "Rohkem kui midagi muud..." ; "Lihalik, surelik tantsib selle ees..." ; "Väike rubiin, mida igaüks ihkab..." ; "Mine heade juurde, kus Armastatugi elab..." ; "Eksitus sulgeb väravad..." ; "Keelilt vallandub helisid..." ; "Kõik algab lahusoleku valust..." ; "Ärka, sõber! Miks ikka veel magad?..." ; "Kuu on mu kehas, kuid ise ma seda ei näe..." ; "Miks oled nii kärsitu, süda?..." ; "Kellele kuulub see flööt..." ; "Kui raske on Külalist kohata!..." ; "Kandetool toodi minule järgi mu isakoju..." ; "Siia ilma sündides nutsid..." ; "Oh mu süda! Ei jõudnud sa tundma õppida..." ; "Õige kulunud on sinu rüü..." ; "Õhkõrn on see õhuke rüü..." ; "Lipp, mida keegi ei näe..." ; "Oh otsija, lihtne liit lähim on südamele..." ; "Õhtu varjud on sügavaks saanud..." ; "Kuis saakski katkeda armastus me kahe vahel..." ; "Luik, tahaksin, et mulle räägiksid kõik oma loo..." ; "Kuhu ihaled küll, minu süda?..." ; "Ei lakka Lõpmatu flöödiheli..." ; "Mida näed, seda pole...". Autori kohta eluloolisi andmeid lk. 11

  12. Phylogenetic reconstruction in the order Nymphaeales: ITS2 secondary structure analysis and in silico testing of maturase k (matK) as a potential marker for DNA bar coding.

    Science.gov (United States)

    Biswal, Devendra Kumar; Debnath, Manish; Kumar, Shakti; Tandon, Pramod

    2012-01-01

    The Nymphaeales (waterlilly and relatives) lineage has diverged as the second branch of basal angiosperms and comprises of two families: Cabombaceae and Nymphaceae. The classification of Nymphaeales and phylogeny within the flowering plants are quite intriguing as several systems (Thorne system, Dahlgren system, Cronquist system, Takhtajan system and APG III system (Angiosperm Phylogeny Group III system) have attempted to redefine the Nymphaeales taxonomy. There have been also fossil records consisting especially of seeds, pollen, stems, leaves and flowers as early as the lower Cretaceous. Here we present an in silico study of the order Nymphaeales taking maturaseK (matK) and internal transcribed spacer (ITS2) as biomarkers for phylogeny reconstruction (using character-based methods and Bayesian approach) and identification of motifs for DNA barcoding. The Maximum Likelihood (ML) and Bayesian approach yielded congruent fully resolved and well-supported trees using a concatenated (ITS2+ matK) supermatrix aligned dataset. The taxon sampling corroborates the monophyly of Cabombaceae. Nuphar emerges as a monophyletic clade in the family Nymphaeaceae while there are slight discrepancies in the monophyletic nature of the genera Nymphaea owing to Victoria-Euryale and Ondinea grouping in the same node of Nymphaeaceae. ITS2 secondary structures alignment corroborate the primary sequence analysis. Hydatellaceae emerged as a sister clade to Nymphaeaceae and had a basal lineage amongst the water lilly clades. Species from Cycas and Ginkgo were taken as outgroups and were rooted in the overall tree topology from various methods. MatK genes are fast evolving highly variant regions of plant chloroplast DNA that can serve as potential biomarkers for DNA barcoding and also in generating primers for angiosperms with identification of unique motif regions. We have reported unique genus specific motif regions in the Order Nymphaeles from matK dataset which can be further validated for

  13. Perspectives on future Alzheimer therapies: amyloid-β protofibrils - a new target for immunotherapy with BAN2401 in Alzheimer's disease.

    Science.gov (United States)

    Lannfelt, Lars; Möller, Christer; Basun, Hans; Osswald, Gunilla; Sehlin, Dag; Satlin, Andrew; Logovinsky, Veronika; Gellerfors, Pär

    2014-01-01

    The symptomatic drugs currently on the market for Alzheimer's disease (AD) have no effect on disease progression, and this creates a large unmet medical need. The type of drug that has developed most rapidly in the last decade is immunotherapy: vaccines and, especially, passive vaccination with monoclonal antibodies. Antibodies are attractive drugs as they can be made highly specific for their target and often with few side effects. Data from recent clinical AD trials indicate that a treatment effect by immunotherapy is possible, providing hope for a new generation of drugs. The first anti-amyloid-beta (anti-Aβ) vaccine developed by Elan, AN1792, was halted in phase 2 because of aseptic meningoencephalitis. However, in a follow-up study, patients with antibody response to the vaccine demonstrated reduced cognitive decline, supporting the hypothesis that Aβ immunotherapy may have clinically relevant effects. Bapineuzumab (Elan/Pfizer Inc./Johnson & Johnson), a monoclonal antibody targeting fibrillar Aβ, was stopped because the desired clinical effect was not seen. Solanezumab (Eli Lilly and Company) was developed to target soluble, monomeric Aβ. In two phase 3 studies, Solanezumab did not meet primary endpoints. When data from the two studies were pooled, a positive pattern emerged, revealing a significant slowing of cognitive decline in the subgroup of mild AD. The Arctic mutation has been shown to specifically increase the formation of soluble Aβ protofibrils, an Aβ species shown to be toxic to neurons and likely to be present in all cases of AD. A monoclonal antibody, mAb158, was developed to target Aβ protofibrils with high selectivity. It has at least a 1,000-fold higher selectivity for protofibrils as compared with monomers of Aβ, thus targeting the toxic species of the peptide. A humanized version of mAb158, BAN2401, has now entered a clinical phase 2b trial in a collaboration between BioArctic Neuroscience and Eisai without the safety concerns seen

  14. The relationship between cholesterol and cognitive function is homocysteine-dependent

    Directory of Open Access Journals (Sweden)

    Cheng YB

    2014-10-01

    Full Text Available Yibin Cheng,1 Yinlong Jin,1 Frederick W Unverzagt,2 Liqin Su,1 Lili Yang,3 Feng Ma,1 Ann M Hake,4,5 Carla Kettler,3 Chen Chen,1 Jingyi Liu,1 Jianchao Bian,6 Ping Li,7 Jill R Murrell,8 Hugh C Hendrie,2,9,10 Sujuan Gao3 1Institute for Environmental Health and Related Product Safety, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China; 2Department of Psychiatry, 3Department of Biostatistics, 4Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA; 5Eli Lilly and Company, Indianapolis, Indiana, USA; 6Shandong Institute for Prevention and Treatment of Endemic Disease in China, Jinan, People’s Republic of China; 7Sichuan Provincial Center for Disease Control and Prevention in China, Chengdu, People’s Republic of China; 8Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 9Indiana University Center for Aging Research, 10Regenstrief Institute, Inc., Indianapolis, Indiana, USA Introduction: Previous studies have identified hyperlipidemia as a potential risk factor for dementia and Alzheimer’s disease. However, studies on cholesterol measured in late-life and cognitive function have been inconsistent. Few studies have explored nonlinear relationships or considered interactions with other biomarker measures.Methods: A cross-sectional sample of 1,889 participants from four rural counties in the People’s Republic of China was included in this analysis. Serum total cholesterol, high-density lipoprotein, triglycerides, and homocysteine levels were measured in fasting blood samples. A composite cognitive score was derived based on nine standardized cognitive test scores. Analysis of covariance models were used to investigate the association between biomarker measures and the composite cognitive scores.Results: There was a significant interaction between the homocysteine quartile group and the cholesterol quartile group on cognitive scores (P=0

  15. The mass-metallicity and fundamental metallicity relations at z > 2 using very large telescope and Subaru near-infrared spectroscopy of zCOSMOS galaxies

    Energy Technology Data Exchange (ETDEWEB)

    Maier, C.; Ziegler, B. L. [Department of Astrophysics, University of Vienna, Türkenschanzstrasse 17, A-1180 Vienna (Austria); Lilly, S. J.; Peng, Y. [Institute of Astronomy, ETH Zurich, Wolfgang-Pauli-Strasse 27, CH-8093 Zurich (Switzerland); Contini, T. [Institut de Recherche en Astrophysique et Planétologie, CNRS, 14 avenue Édouard Belin, F-31400 Toulouse (France); Pérez Montero, E. [Instituto de Astrofísica de Andalucia, CSIC, Apartado de Correos 3004, E-18080 Granada (Spain); Balestra, I., E-mail: christian.maier@univie.ac.at [Max-Planck-Institut für Extraterrestrische Physik, Postfach 1312, Giessenbachstrasse, D-85741 Garching b. München (Germany)

    2014-09-01

    In the local universe, there is good evidence that, at a given stellar mass M, the gas-phase metallicity Z is anti-correlated with the star formation rate (SFR) of the galaxies. It has also been claimed that the resulting Z(M, SFR) relation is invariant with redshift—the so-called 'fundamental metallicity relation' (FMR). Given a number of difficulties in determining metallicities, especially at higher redshifts, the form of the Z(M, SFR) relation and whether it is really independent of redshift is still very controversial. To explore this issue at z > 2, we used VLT-SINFONI and Subaru-MOIRCS near-infrared spectroscopy of 20 zCOSMOS-deep galaxies at 2.1 < z < 2.5 to measure the strengths of up to five emission lines: [O II] λ3727, Hβ, [O III] λ5007, Hα, and [N II] λ6584. This near-infrared spectroscopy enables us to derive O/H metallicities, and also SFRs from extinction corrected Hα measurements. We find that the mass-metallicity relation (MZR) of these star-forming galaxies at z ≈ 2.3 is lower than the local Sloan Digital Sky Survey (SDSS) MZR by a factor of three to five, a larger change than found by Erb et al. using [N II]/Hα-based metallicities from stacked spectra. We discuss how the different selections of the samples and metallicity calibrations used may be responsible for this discrepancy. The galaxies show direct evidence that the SFR is still a second parameter in the MZR at these redshifts. However, determining whether the Z(M, SFR) relation is invariant with epoch depends on the choice of extrapolation used from local samples, because z > 2 galaxies of a given mass have much higher SFRs than the local SDSS galaxies. We find that the zCOSMOS galaxies are consistent with a non-evolving FMR if we use the physically motivated formulation of the Z(M, SFR) relation from Lilly et al., but not if we use the empirical formulation of Mannucci et al.

  16. Risk factors associated with metabolic syndrome in type 2 diabetes mellitus patients according to World Health Organization, Third Report National Cholesterol Education Program, and International Diabetes Federation definitions

    Directory of Open Access Journals (Sweden)

    Angel Rodríguez

    2010-12-01

    Full Text Available Angel Rodríguez1, Helena Delgado-Cohen1, Jesús Reviriego1, Manuel Serrano-Ríos21Clinical Research Department, Eli Lilly and Company, Madrid, Spain; 2Department of Internal Medicine II, Hospital Clinico San Carlos, Madrid, SpainBackground: The availability of several definitions of the metabolic syndrome has created potential confusion concerning its prognostic utility. At present, little data exist about the risk factors associated with metabolic syndrome in diabetic patients.Aim: To identify risk factors associated with metabolic syndrome in patients with type 2 diabetes mellitus according to three diagnostic criteria: World Health Organization (WHO, Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults – Adult Treatment Panel III (NCEP-ATP III, and International Diabetes Federation (IDF.Subjects and methods: A logistic regression model was used to identify demographic, clinical, and lifestyle variables related with metabolic syndrome (N = 1259.Results: Hypertension, dyslipidemia, and glycosylated hemoglobin (HbA1c ≥7% were associated with increased risk of WHO-defined metabolic syndrome (odds ratio [OR], 2.33; 95% confidence interval [CI]: 1.60–3.40; OR, 1.79 95% CI: 1.25–2.55; and OR, 1.58; 95% CI: 1.12–2.22, respectively. The risk of presenting metabolic syndrome according to NCEP-ATP III criteria was increased in female patients (OR, 2.02; 95% CI: 1.37–2.97, elevated fasting glucose levels (OR, 5.99; 95% CI: 3.56–10.07, dyslipidemia (OR, 2.28; 95% CI: 1.57–3.32, hypertension (OR, 2.36; 95% CI: 1.59–3.53, and endocrine disorders (OR, 1.64; 95% CI: 1.06–2.57. For the IDF criteria, female patients and patients with left ventricular hypertrophy or insulin treatment were at higher risk of metabolic syndrome (OR, 4.00; 95% CI: 2.35–6.80; OR, 2.72 95% CI: 1.22–6.04; and OR, 1.96 95% CI: 1.24–3.11, respectively.Conclusions: The

  17. Cost-effectiveness of pemetrexed in combination with cisplatin as first line treatment for patients with advanced non-squamous non-small-cell

    Directory of Open Access Journals (Sweden)

    Jonathan González García

    2017-01-01

    Full Text Available Introduction: Lung cancer is the third most frequent neoplastic tumour in Spain, with around 27 000 new cases diagnosed per year; 80-95% of these are non-small-cell cancer (NSCLC, and the majority of cases are diagnosed in advanced stages of the disease, and for this reason it is one of the oncologic conditions with higher mortality rates (21.4% mean survival at 5 years. The main treatment regimens used for first-line treatment of NSCLC are: isplatin/pemetrexed (cis/pem, cisplatin/gemcitabine/ bevacizumab (cis/gem/bev, and carboplatin/paclitaxel/ bevacizumab (carb/pac/bev. The objective of this study was to evaluate the cost-effectiveness ratio of antineoplastic 1st line NSCLC treatment regimens, from the point of view of hospital management. Methodology: A cost-efficacy mathematical model was prepared, based on a decision tree. The efficacy variable was Progression Free Survival, obtained from the PARAMOUNT, AVAIL and SAIL Phase III clinical trials. The study was conducted from the perspective of the hospital management, considering only the direct costs of drug acquisition. A deterministic sensitivity analysis was conducted to confirm the robustness of outcomes. Results: The PFS obtained in clinical trials with cis/pem, cis/ gem/bev and carb/pac/bev was: 6.9, 6.7 and 6.2 months, respectively. Based on our model, the mean cost of treatment per patient for these regimens was: 19 942 €, 15 594 € and 36 095 €, respectively. The incremental cost-effectiveness ratio per month of additional PFS between cis/pem and cis/gem/bev was 19 303 €. Estimating a 30% reduction in acquisition costs for pemetrexed (Alimta®Eli Lilly Nederland B.V., due to the forthcoming launch of generic medications, the cis/pem treatment would become the predominant alternative for 1st line treatment of NSCLC patients, by offering the best health results at a lower cost.

  18. Cost of medication adherence and persistence in type 2 diabetes mellitus: a literature review

    Directory of Open Access Journals (Sweden)

    Kennedy-Martin T

    2017-06-01

    Full Text Available Tessa Kennedy-Martin,1 Kristina S Boye,2 Xiaomei Peng2 1Kennedy-Martin Health Outcomes Ltd, Brighton, UK; 2Global Health Outcomes, Eli Lilly and Company, Indianapolis, IN, USA Purpose: To explore published evidence on health care costs associated with adherence or persistence to antidiabetes medications in adults with type 2 diabetes mellitus (T2DM.Methods: Primary research studies published between January 2006 and December 2015 on compliance, adherence, or persistence and treatment in patients with T2DM that document a link with health care costs were identified through literature searches in bibliographic databases and 2015 abstract books for relevant DM congresses. Results were assessed for relevance by two reviewers. The review was part of a larger overview evaluating the impact of adherence and persistence on a range of clinical and economic outcomes; only findings from the cost element are reported herein.Results: A total of 4,662 de-duplicated abstracts were identified and 110 studies included in the wider review. Of these, 19 reported an association between adherence (n=13, persistence (n=5, or adherence and persistence (n=1, and health care costs. All studies were retrospective, with sample sizes ranging from 301 to 740,195. Medication possession ratio was the most commonly employed adherence measure (n=11. The majority of adherence studies (n=9 reported that medication adherence was associated with lower total health care costs. Pharmacy costs were often increased in adherent patients but this was offset by beneficial effects on other costs. Findings were more variable in persistence studies; three reported that higher pharmacy costs in persistent patients were not sufficiently offset by savings in other areas to result in a reduction in total health care costs.Conclusions: Few studies have evaluated the relationship between adherence, persistence, and health care costs in T2DM. However, it has been consistently shown that medication

  19. Utilization Patterns of Glucagon-Like Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes Mellitus in Italy: A Retrospective Cohort Study.

    Science.gov (United States)

    Federici, Marco Orsini; McQuillan, Janette; Biricolti, Giovanni; Losi, Serena; Lebrec, Jeremie; Richards, Catrina; Miglio, Cristiana; Norrbacka, Kirsi

    2018-04-01

    treatments, patients prescribed exBID recorded the lowest and those prescribed DULA the highest persistence with therapy. Eli Lilly and Co., Indianapolis, IN, USA.

  20. Evaluating preferences for profiles of GLP-1 receptor agonists among injection-naïve type 2 diabetes patients in the UK

    Directory of Open Access Journals (Sweden)

    Gelhorn HL

    2015-11-01

    Full Text Available Heather L Gelhorn,1 Jiat-Ling Poon,1 Evan W Davies,2 Rosirene Paczkowski,3 Sarah E Curtis,3 Kristina S Boye3 1Outcomes Research, Evidera, Bethesda, MD, USA; 2Outcomes Research, Evidera, London, UK; 3Global Patient Outcomes and Real World Evidence, Eli Lilly and Company, Indianapolis, IN, USA Objective: To use a discrete choice experiment (DCE to evaluate preferences for the actual treatment features and overall profiles of two injectable glucagon-like peptide-1 receptor agonists (dulaglutide and liraglutide among patients with type 2 diabetes mellitus (T2DM in the UK.Methods: In-person interviews were conducted in the UK to administer a DCE to patients with self-reported T2DM, naïve to treatment with injectable medications. The DCE examined six attributes of T2DM treatment each described by two levels: “dosing frequency,” “hemoglobin A1c change,” “weight change,” “type of delivery system,” “frequency of nausea,” and “frequency of hypoglycemia.” Part-worth utilities were estimated using random effects logit models and were used to calculate relative importance (RI values for each attribute. A chi-square test was used to determine differences in preferences for dulaglutide versus liraglutide profiles.Results: A total of 243 participants [mean age: 60.5 (standard deviation 10.9 years; 76.1% male; mean body mass index: 29.8 (standard deviation 5.4 kg/m2] completed the study. RI values for the attributes in rank order were: “dosing frequency” (41.6%, “type of delivery system” (35.5%, “frequency of nausea” (10.4%, “weight change” (5.9%, “hemoglobin A1c change” (3.6%, and “frequency of hypoglycemia” (3.0%. Significantly more participants preferred the dulaglutide profile (83.1% compared with the liraglutide profile (16.9%; P<0.0001.Conclusion: This study elicited patients’ preferences for attributes and levels representing the actual characteristics of two specific glucagon-like peptide-1 medications

  1. Characteristics, Treatment Patterns, and Economic Outcomes of Patients Initiating Injectable Medications for Management of Type 2 Diabetes Mellitus in Japan: Results from a Retrospective Claims Database Analysis.

    Science.gov (United States)

    Suzuki, Shuichi; Desai, Urvi; Strizek, Alena; Ivanova, Jasmina; Garcia-Horton, Viviana; Cai, Zhihong; Schmerold, Luke; Liu, Xinyue; Perez-Nieves, Magaly

    2018-04-16

    antidiabetics were largely prescribed by GPs. Future research should evaluate the factors associated with different provider practices and communication channels between specialists and GPs to improve patient management. Eli Lilly and Co.

  2. Residual symptoms in patients with partial versus complete remission of a major depressive disorder episode: patterns of painful physical symptoms in depression

    Directory of Open Access Journals (Sweden)

    Harada E

    2016-06-01

    Full Text Available Eiji Harada,1 Yoichi Satoi,2 Toshiaki Kikuchi,3 Koichiro Watanabe,3 Levent Alev,1 Masaru Mimura4 1Medical Science, Medicines Development Unit-Japan, 2Statistical Science, Medicines Development Unit-Japan, Eli Lilly Japan K.K., Kobe, Hyogo, 3Department of Neuropsychiatry, Kyorin University School of Medicine, 4Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan Objective: The patterns of residual painful physical symptoms (PPS and emotional symptoms among patients with partial remission (PR or complete remission (CR of a major depressive disorder (MDD episode were compared. Methods: This is a multicenter, cross-sectional, observational study. Patients who had originally been diagnosed with MDD, were treated with an antidepressant for 12 weeks for that episode, and achieved either PR or CR at study entry were enrolled in the study. Using the 17-item Hamilton Rating Scale for Depression (HAM-D17, PR was defined as a score of ≥8 and ≤18 and CR as a score of ≤7. Residual symptoms were assessed using the Brief Pain Inventory-Short Form (BPI-SF and the HAM-D17.Results: A total of 323 patients (CR =158, PR =165 were included in the study. Patients in the PR group had a higher mean (standard deviation score in the HAM-D17 than those in the CR group (11.8 [3.1] and 4.4 [2.0], respectively. BPI-SF results showed that “at least moderate PPS” (score ≥3 on BPI-SF question 5 was significantly more prevalent among patients with PR than those with CR (37.0% vs 16.5%, respectively; odds ratio =3.04; P<0.001. Presence of pain (any severity was also more prevalent among patients with PR than those with CR (54.5% vs 35.4%, respectively. The HAM-D17 results for individual items indicated that impaired work and activities, depressed mood, psychological and somatic anxiety, and general somatic symptoms were observed in at least 75% of patients with PR.Conclusion: PR was associated with a higher prevalence of at least moderate PPS

  3. Long-acting injectable antipsychotics: focus on olanzapine pamoate

    Directory of Open Access Journals (Sweden)

    JP Lindenmayer

    2010-05-01

    Full Text Available JP LindenmayerDepartment of Psychiatry, New York University School of Medicine, New York NY, USAAbstract: Medication non-adherence in patients with schizophrenia continues to be a significant problem and threatens successful treatment outcomes. Medication non-adherence is often associated with negative consequences, including symptom exacerbation, more frequent emergency room visits, re-hospitalizations and relapse. Long-acting injectable (LAI forms of antipsychotics allow for rapid identification of non-adherence, obviate the need for the patient to take the medication on a daily basis and increase adherence to some significant degree. Eli Lilly has developed a long-acting depot formulation of olanzapine, olanzapine pamoate, which has recently been approved by the FDA for the US market, and which will be reviewed here. Olanzapine LAI appears to be an effective antipsychotic at dosages of 210 mg every 2 weeks, 300 mg every 2 weeks and 405 mg every 4 weeks in patients with acute schizophrenia, and at 150 mg every 2 weeks, 300 mg every 2 weeks and at 405 mg every 4 weeks for the maintenance treatment of stable patients. Oral supplementation appears not to be needed, particularly not at the onset of treatment with the LAI as is necessary with risperidone LAI. Its efficacy is in general comparable to the efficacy seen with oral olanzapine at a corresponding dose. The side effect profile is also comparable to the side effects observed with oral olanzapine, including lower rates of extrapyramidal symptoms, prolactin elevation and cardiovascular side effects, but significant metabolic effects. The latter include significant weight gain, lipid abnormalities and glucose dysregulation. While the injection site adverse events are overall mild, the most significant serious adverse event is the post-injection delirium sedation syndrome (PDSS. While rare, this syndrome results from inadvertent intravascular injection of olanzapine LAI and can cause a range of

  4. Diabetes mellitus and insulin in an aspirin sensitive asthmatic.

    Science.gov (United States)

    Caplin, I

    1976-03-01

    The infrequency of diabetes mellitus and asthma in the same individual is re-examined. The antagonism between epinephrine and insulin, as suggested by Konig in 1935, is indeed accurate. The assays done by the Eli Lilly Research Department revealed no in vitro effect of insulin on the CAMP and GMP level of mast cells as occurs in liver cells. It is felt that this effect is probably an in vivo effect produced via the vagus nerve and alpha-adrenergic receptor system stimulation. This would explain the mechanism of aggravation of asthma by excess insulin. Dr. Petersen's studies, the negative intradermal skin tests to insulin and the absence of change on either beef or pork insulin usage by our patient all point to a nonatopic factor in the aggravation of the asthma of this patient. In the uncommon occurrence of asthma and diabetes in the same patient, insulin dosage should be considered as a factor in all such asthmatics who do not respond well to conventional therapy. Two additional asthmatics who also have diabetes did improve with cessation of nocturnal asthma by a reduction of their evening dose of insulin. A high fat, low carbohydrate diet, as suggested by Abrahamson to avoid dietary hyperinsulinism, is certainly worth considering in patients with nocturnal asthma. If patients cannot be made to follow a diet requiring frequent feedings high in protein and fats and low in carbohydrates, another approach suggests itself. Abrahamson was able to relieve the patients who developed nocturnal asthma with hypoglycemia by having them drink a glass of milk. Assuming other causes have been eliminated and a patient awakens each day at 3:00 a.m., an alarm clock could be set at 2:00 a.m. Milk or a milk substitute in milk sensitive patients could be taken at 2:00 a.m. to raise the blood sugar and hopefully prevent the asthma associated with hypoglycemia. Also to be noted is the ubiquitous use of tartrazine in so many drugs, including those used to relieve asthmatic symptoms

  5. Learn, how to learn

    Science.gov (United States)

    Narayanan, M.

    2002-12-01

    . Maintain Momentum. 13. Feedback : Communication. 14. Fact - Based Decisions. 15. Exploit Opportunities. 16. Mobilization of Expertise. 17. Drive out Fear. 18. Recognition / Keep Score. 19. Identify Accomplishments. 20. Customer Focus / Results. In conclusion, the author believes that the ACORN model and the QUOTES model may offer some guidelines that would help and enable the instructor to motivate learners to learn on their own. References Boyer, Ernest L. (1990). Scholarship reconsidered: Priorities of the Professorate. Princeton, NJ: Carnegie Foundation for the Advancement of Teaching. Hawkins, P., and Winter, J. (1997). Mastering change: Learning the lessons of the enterprise in higher education initiative. London: Department for Education and Employment. Narayanan, Mysore (2002). Total Quality Management (TQM) and the Teaching Professor. Oxford, Ohio. : Mimi University : 22nd Annual Lilly Conference on College Teaching.

  6. Long-term survival in advanced melanoma patients using repeated therapies: successive immunomodulation improving the odds?

    Directory of Open Access Journals (Sweden)

    Coventry BJ

    2015-04-01

    Full Text Available Brendon J Coventry, Dominique Baume, Carrie Lilly Discipline of Surgery, Royal Adelaide Hospital, University of Adelaide, Adelaide, SA, Australia Background: Patients with advanced metastatic melanoma are often confronted with little prospect of medium- to longer-term survival by any currently available therapeutic means. However, most clinicians are aware of exceptional cases where survival defies the notion of futility. Prolonged survival from immunotherapies, including interleukin-2, vaccines and antibodies to cytotoxic lymphocyte antigen-4, and programmed death-1 receptor inhibitory monoclonal antibody, implies a role for immune system modulation. We aimed to identify cases where exceptional survival from advanced melanoma occurred prior to recent novel therapies to facilitate better understanding of this phenomenon. Methods: Cases of long-term survival of ≥3 years' duration (from diagnosis of metastatic disease were identified from the database of one clinician; these cases were treated before the availability of newer immunotherapies, and they were documented and examined. A literature search for reported outcome measures from published studies using older and recent therapies for advanced melanoma was conducted to enable the comparison of data. Results: Eighteen cases were identified that identified survival of ≥3 years' duration from metastatic disease (12 American Joint Committee on Cancer [AJCC] Stage IV cases; six AJCC III cases diagnosis. These were assessed and reported to detail the clinical course. Standard clinical prognostication methods predicted high risk of early mortality in those patients. No identifiable differences could be detected between these and other patients with similar patterns of disease. At evaluation, 17 patients (94% had survived ≥5 years, and eleven patients (61% had survived ≥10 years (range: 3–15 years. The median survival duration with metastatic disease was 11 years; 15 remained alive and three

  7. Real-world comparison of health care utilization between duloxetine and pregabalin initiators with fibromyalgia

    Directory of Open Access Journals (Sweden)

    Peng X

    2014-01-01

    Full Text Available X Peng,1 P Sun,2 D Novick,1 J Andrews,1 S Sun2 1Eli Lilly and Company, Indianapolis, IN, USA; 2Kailo Research Group, Indianapolis, IN, USA Objectives: To compare health care utilization of duloxetine initiators and pregabalin initiators among fibromyalgia patients in a real-world setting. Methods: A retrospective cohort study was conducted based on a US national commercial health claims database (2006–2009. Fibromyalgia patients who initiated duloxetine or pregabalin in 2008, aged 18–64 years, and who maintained continuous health insurance coverage 1 year before and 1 year after initiation were assigned to duloxetine or pregabalin cohorts on the basis of their initiated agent. Patients who had pill coverage of the agents over the course of 90 days preceding the initiation were excluded. The two comparative cohorts were constructed using propensity score greedy match methods. Descriptive analysis and paired t-test were performed to compare health care utilization rates in the postinitiation year and the changes of these rates from the preinitiation year to the postinitiation year. Results: Both matched cohorts (n=1,265 pairs had a similar mean initiation age (49–50 years, percentage of women (87%–88%, and prevalence of baseline comorbid conditions (neuropathic pain other than diabetic peripheral neuropathic pain, low back pain, cardiovascular disease, hypertension, headache or migraine, and osteoarthritis. In the preinitiation year, both cohorts had similar inpatient, outpatient, and medication utilization rates (inpatient, 15.7%–16.1%; outpatient, 100.0%; medication, 97.9%–98.7%. The utilization rates diverged in the postinitiation year, with the pregabalin cohort using more fibromyalgia-related inpatient care (3.2% versus 2.2%; P<0.05, any inpatient care (19.3% versus 16.8%; P<0.05, and fibromyalgia-related outpatient care (62.1% versus 51.8%; P<0.05. From the preinitiation period to the postinitiation period, the duloxetine cohort

  8. Systematic review of the use of bone turnover markers for monitoring the response to osteoporosis treatment: the secondary prevention of fractures, and primary prevention of fractures in high-risk groups.

    Science.gov (United States)

    Burch, Jane; Rice, Stephen; Yang, Huiqin; Neilson, Aileen; Stirk, Lisa; Francis, Roger; Holloway, Paul; Selby, Peter; Craig, Dawn

    2014-02-01

    There is currently no standard practice for the monitoring of patients receiving treatment for osteoporosis. Repeated dual-energy X-ray absorptiometry (DXA) is commonly used for monitoring treatment response, but it has its limitations. Bone turnover markers have advantages over DXA as they are non-invasive, relatively cheap and can detect changes in bone turnover rates earlier. However, they do have disadvantages, particularly high within- and between-patient variability. The ability of bone turnover markers to identify treatment non-responders and predict future fracture risk has yet to be established. We aimed to determine the clinical effectiveness, test accuracy, reliability, reproducibility and cost-effectiveness of bone turnover markers for monitoring the response to osteoporosis treatment. We searched 12 electronic databases (including MEDLINE, EMBASE, The Cochrane Library and trials registries) without language restrictions from inception to March 2012. We hand-searched three relevant journals for the 12 months prior to May 2012, and websites of five test manufacturers and the US Food and Drug Administration (FDA). Reference lists of included studies and relevant reviews were also searched. A systematic review of test accuracy, clinical utility, reliability and reproducibility, and cost-effectiveness of two formation and two resorption bone turnover markers, in patients being treated for osteoporosis with any of bisphosphonate [alendronate (Fosamax, MSD), risedronate (Actonel, Warner Chilcott Company), zolendronate (Zometa, Novartis)], raloxifene (Evista, Eli Lilly and Company Ltd), strontium ranelate (Protelos, Servier Laboratories Ltd), denosumab (Prolia, Amgen Ltd) or teriparatide (Forsteo, Eli Lilly and Company Ltd), was undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Given the breadth of the review question, a range of study designs and outcome measures were eligible. The development

  9. Especially for High School Teachers

    Science.gov (United States)

    Howell, J. Emory

    1999-07-01

    Secondary School Feature Articles * Super Science Connections, by Patricia B. McKean, p 916 * A pHorseshoe, by Roger Plumsky, p 935 National Conferences in Your Part of the Country For the past several months, considerable space in this column has been devoted to forthcoming national conferences and conventions and to highlights of conferences past. For some of us, location is fairly unimportant; but for most of us travel costs and time are both factors to consider when choosing a conference. The community of high school chemistry teachers is favored by the number of national conventions and conferences that are held each year in different locations. In 1999, for example, the spring National Meeting of the American Chemical Society was in Anaheim and the National Science Teachers Association National Convention was in Boston. This summer CHEMED '99 will be held in Fairfield, CT, August 1-5, and the fall National ACS Meeting will be in New Orleans. Teachers from the mid-South especially should consider attending the High School Program at New Orleans, described below by Lillie Tucker Akin, Chairperson of the Division's High School Program Committee. The event will be held on Sunday to minimize conflicts with the beginning of the school year. JCE at CHEMED '99 Stop by the JCE booth at CHEMED '99 in the exhibits area to learn more about the wide array of print and nonprint resources you can use in your classroom and laboratory. Members of the editorial staff will be on hand to talk with you. You are invited to participate in a workshop, "Promoting Active Learning through JCE Activity Sheets and Software", on Monday, August 1, 8:30-10:30. The free hands-on workshop is number WT11 and we encourage you to include it among your choices in the blanks provided on the third page of the registration form. We will also conduct an interactive session to listen to ideas for making the Journal more useful to you. Check the final program for location and time or inquire at the JCE

  10. Quality rating of MR-cholangiopancreatography with oral application of iron oxide particles; Wertigkeit der MR-Cholangiopankreatikographie nach Gabe eines oralen eisenhaltigen Kontrastmittels

    Energy Technology Data Exchange (ETDEWEB)

    Lorenzen, M.; Wedegaertner, U.; Fiehler, J.; Adam, G. [Universitaetsklinikum Hamburg, Klinik und Poliklinik fuer Diagnostische und Interventionelle Radiologie (Germany)

    2003-07-01

    Purpose: To compare image quality in magnetic resonance cholangiopancreatography (MRCP) performed with and without oral application of Loesferron {sup trademark} (ferrous gluconate, Lilly Pharma, Hamburg). Materials and Methods: A prospective study compares MRCPs performed on 52 patients with a 1.5 T clinical whole body scanner using a standard body coil. After randomization, patients ingested either 0.5 l of Loeseferron {sup trademark} (n=27, group 1) or no oral contrast agent (n=25, group 2) prior to the examination. 7 RARE (40 to 20 ) sequences were obtained, followed by selected 3 mm HASTE (T{sub 2}-weighted with fat suppression) sequences. After blinding, image quality was rated by two radiologists using a scale of 1 (not discernible) to 5 (very well discernible). The following sections of the biliary ductal system were evaluated: left and right hepatic duct, extrahepatic bile duct and intrapancreatic bile duct. The pancreatic duct was evaluated by its location: head, body and tail of the pancreas. A Wilcoxon-Mann-Whitney test was used to determine significant differences (p<0.05) between sampled ductal segments. Correction for multiple testing was applied. Results: The oral application of Loeseferron {sup trademark} was well tolerated by all patients, and all sequences could be acquired and evaluated in all 52 patients. For the different sections of the biliary system, the mean ratings with and without Loesferron {sup trademark} were, respectively, 3.28 and 3.36 for the left hepatic duct, 3.26 and 3.33 for the right hepatic duct, 3.46 and 4.0 for the extrahepatic bile duct, and 2.8 and 3.48 for the intrapancreatic bile duct. The corresponding ratings for the pancreatic duct were 2.8 and 3.24 for the pancreatic head, 2.84 and 3.38 for the pancreatic body, and 2.68 and 3.22 for the pancreatic tail. The differences with and without contrast agent were not statistically significant. Interobserver variability was between 0.37 for the pancreatic duct in the tail of

  11. Importance of Technical Writing in Engineering Education

    Science.gov (United States)

    Narayanan, M.

    2010-12-01

    ., Grasha, A., & Richlin, L. (1997, March). Town meeting. Between teaching model and learning model: Adapting and adopting bit by bit. Paper presented at the ninth annual Lilly Conference on College and University Teaching - West, Lake Arrowhead, CA. Narayanan, Mysore (2009). Assessment Based on the principles of Theodore Marchese. ASEE 116th Annual Conference and Exposition, Austin, TX. June 14-17, 2009. Paper # AC 2009-1532. Saxe, S. (1990, June). Peer influence and learning. Training and Development Journal, 42 (6), 50-53. Senge, P. M. (1990). The fifth discipline: The art and practice of the learning organization. New York: Currency Doubleday. Sims, R. R. (1992, Fall). Developing the learning climate in public sector training programs. Public Personnel Management, 21 (3), 335-346. Kosakowski, John, (1998). The Benefits of Information Technology. ERIC Digests; Technology Integration; Technology Role, ED0-IR-98-04 Chaika, Gloria (2000), Encourage Student Writing: Published on the Web, Education World http://www.education-world.com/a_tech/tech042.shtml

  12. Impact of the 2013 Cholesterol Guideline on Patterns of Lipid-Lowering Treatment in Patients with Atherosclerotic Cardiovascular Disease or Diabetes After 1 Year.

    Science.gov (United States)

    Tran, Josephine N; Kao, Tzu Chun; Caglar, Toros; Stockl, Karen M; Spertus, John A; Lew, Heidi C; Solow, Brian K; Chan, Paul S

    2016-08-01

    untreated or undertreated. No outside funding supported this research. Chan is supported by grants from the National Heart Lung and Blood Institute (1R01HL123980 and K23HL102224). Tran, Stockl, Lew, and Solow are employed by Optum. Kao and Caglar were employed by Optum when this study was conducted. Chan serves as an advisor and consultant to OptumRx but received no compensation for work on this manuscript. Stockl is also employed by the Journal of Managed Care & Specialty Pharmacy. Spertus reports personal fees from United Healthcare and grants from Lilly, outside of the submitted work. None of the authors have any other financial conflicts of interest to report. Tran and Chan supervised this study, had full access to all of the data in the study, and take responsibility for the integrity of the data and the accuracy of the data analysis. Study design and concept were contributed by Tran and Chan. Tran and Kao collected the data, with analysis and interpretation performed by all the authors. Statistical analysis was performed by Caglar and Kao, and Tran and Chan drafted the manuscript. All authors were involved in the critical revision of the manuscript.

  13. Classroom Assessment Techniques

    Science.gov (United States)

    Narayanan, M.

    2003-12-01

    and the learner should be carefully observed and monitored. Forrest says that Student Portfolios, which document learning in more detail, seldom reveal how teaching contributes to students' progress. Cerbin further indicates that a course portfolio is essentially, a like a manuscript of scholarly work in progress. In this example, it is a work that explains what, how, and why students learn or do not learn in a course. In this paper, the author reports on a dozen techniques that could perhaps be used to document assessment of student learning. References : Cerbin, W. (1993). Fostering a culture of teaching as scholarship. The Teaching Professor, 7(3), 1-2. Edgerton, R., Hutchings, P., & Quinlan, P. (1991). The teaching portfolio: Capturing the scholarship in teaching. Washington, DC: American Association for Higher Education. Forrest, A. (1990). Time will tell: Portfolio-assisted assessment of general education. Washington, DC: American Association for Higher Education. Linn, R., Baker, E., & Dunbar, S. (1991). Complex, Performance-based Assessment: Expectations and Validation Criteria. Educational Researcher, 20 (8), 15-21. Narayanan, M. (2003). Assessment in Higher Education: Partnerships in Learning. Paper presented at the 23rd Annual Lilly Conference on College Teaching, Miami University, Oxford, OH. Seldin, P. (1991). The teaching portfolio. Bolton, MA: Anker. Young, C. O., Sr., & Young, L. H. (1999). Assessing Learning in Interactive Courses. Journal on Excellence in College Teaching, 10 (1), 63-76.

  14. Exploring Our Low-Mass Neighbors

    Science.gov (United States)

    Kohler, Susanna

    2017-10-01

    on the other two data sets. [Bralts-Kelly et al. 2017]The students used the VLA to obtain neutral hydrogen spectral-line observations of UGC 11411 and UGC 8245 in February and March of this year. They then processed and analyzed the data, exploring the stellar population and star formation in each galaxy, and using the galaxies bulk kinematics to calculate their total dynamical masses.Dominated by Dark MatterThe authors found that in both galaxies, the greatest bulk of the neutral interstellar medium can be found in the same location as the ongoing star formation. The two galaxies are different in several ways, however: UGC 8245 has a much lower star formation rate than UGC 11411 currently, and though the neutral hydrogen gas and stellar masses are similar for both galaxies, UGC 11411 has a halo that is more than an order of magnitude more massive.They conclude that UGC 8245 which has a total mass that is only 2 times larger than its baryonic mass is very similar to other low-mass galaxies that have been studied in the past. On the other hand, UGC 11411 which has a total mass that is at least a factor of 10 larger than its baryonic mass is significantly more massive than other known local low-mass galaxies, and it is unusually highly dark-matter dominated.Further explorations of these dwarfs in contrast to one another will continue to reveal information about the low-mass galaxies of the universe.CitationLilly Bralts-Kelly et al 2017 ApJL 848 L10. doi:10.3847/2041-8213/aa8ea0

  15. Effects of empagliflozin on the urinary albumin-to-creatinine ratio in patients with type 2 diabetes and established cardiovascular disease: an exploratory analysis from the EMPA-REG OUTCOME randomised, placebo-controlled trial.

    Science.gov (United States)

    Cherney, David Z I; Zinman, Bernard; Inzucchi, Silvio E; Koitka-Weber, Audrey; Mattheus, Michaela; von Eynatten, Maximilian; Wanner, Christoph

    2017-08-01

    and 1338 assigned to empagliflozin) had microalbuminuria, and 769 (11%; 260 assigned to placebo and 509 assigned to empagliflozin) had macroalbuminuria. Median treatment duration was 2·6 years (IQR 2·0-3·4; 136 weeks) and median observation time was 3·1 years (2·2-3·6; 164 weeks). After short-term treatment at week 12, the placebo-adjusted geometric mean ratio of UACR change from baseline with empagliflozin was -7% (95% CI -12 to -2; p=0·013) in patients with normoalbuminuria, -25% (-31 to -19; pratio of relative change from baseline with empagliflozin: -22%, 95% CI -32 to -11; p=0·0003) or macroalbuminuria (-29%, -44 to -10; p=0·0048), but not for patients with baseline normoalbuminuria (1%, -8 to 10; p=0·8911). Patients treated with empagliflozin were more likely to experience a sustained improvement from microalbuminuria to normoalbuminuria (hazard ratio [HR] 1·43, 95% CI 1·22 to 1·67; p<0·0001) or from macroalbuminuria to microalbuminuria or normoalbuminuria (HR 1·82, 1·40 to 2·37; p<0·0001), and less likely to experience a sustained deterioration from normoalbuminuria to microalbuminuria or macroalbuminuria (HR 0·84, 0·74 to 0·95; p=0·0077). The proportions of patients with any adverse events, serious adverse events, and adverse events leading to discontinuation increased with worsening UACR status at baseline, but were similar between treatment groups. The proportion of patients with genital infections was greater with empagliflozin than placebo in all subgroups by UACR status. These results support short-term and long-term benefits of empagliflozin on urinary albumin excretion, irrespective of patients' albuminuria status at baseline. Boehringer Ingelheim & Eli Lilly and Company Diabetes Alliance. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. A single-dose, randomized, two-way crossover study comparing two olanzapine tablet products in healthy adult male volunteers under fasting conditions.

    Science.gov (United States)

    Elshafeey, Ahmed H; Elsherbiny, Mohamed A; Fathallah, Mohsen M

    2009-03-01

    Olanzapine is a psychotropic agent that belongs to the thienobenzodiazepine class. The aim of this study was to assess the bioequivalence of 2 commercial 10-mg tablet formulations of olanzapine by statistical analysis of the pharmacokinetic parameters C(max), AUC from 0 to 72 hours after dosing (AUC(0-72)), and AUC(0-infinity) as required by the Egyptian health authority for the marketing of a generic product. This bioequivalence study was carried out in healthy male volunteers using a single-dose, randomized, 2-way crossover design under fasting conditions. Statistical analysis of the pharmacokinetic parameters C(max), AUC(0-72), and AUC(0-infinity) was conducted to determine bioequivalence (after log-transformation of data using analysis of variance and 90% CIs) and to gain marketing approval in Egypt. The formulations were considered to be bioequivalent if the log-transformed ratios of the 3 pharmacokinetic parameters were within the predetermined bioequivalence range (ie, 80%-125%), as established by the US Food and Drug Administration (FDA). Both the test product (Trademark: Integrol((R)) [Global Napi Pharmaceuticals, Cairo, Egypt]) and the reference product (Trademark: Zyprexa((R)) [Eli Lilly and Company, Basingstoke, Hampshire, United Kingdom]) were administered as 10-mg tablets with 240 mL of water after an overnight fast on 2 treatment days, separated by a 2-week washout period. After dosing, serial blood samples were collected for 72 hours. Plasma samples were analyzed using a sensitive, reproducible, and accurate liquid chromatography-tandem mass spectrometry method capable of quantitating olanzapine in the range of 0.167 to 16.7 ng/mL, with a lower limit of quantitation of 0.167 ng/mL. Adverse events were reported by the volunteers as instructed or observed by the resident physician, and were recorded, tabulated, and evaluated. Twenty-four healthy adult male volunteers participated in this study. Their mean (SD) age was 24.7 (6.2) years (range, 19

  17. Ramucirumab for Treating Advanced Gastric Cancer or Gastro-Oesophageal Junction Adenocarcinoma Previously Treated with Chemotherapy: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

    Science.gov (United States)

    Büyükkaramikli, Nasuh C; Blommestein, Hedwig M; Riemsma, Rob; Armstrong, Nigel; Clay, Fiona J; Ross, Janine; Worthy, Gill; Severens, Johan; Kleijnen, Jos; Al, Maiwenn J

    2017-12-01

    The National Institute for Health and Care Excellence (NICE) invited the company that manufactures ramucirumab (Cyramza ® , Eli Lilly and Company) to submit evidence of the clinical and cost effectiveness of the drug administered alone (monotherapy) or with paclitaxel (combination therapy) for treating adults with advanced gastric cancer or gastro-oesophageal junction (GC/GOJ) adenocarcinoma that were previously treated with chemotherapy, as part of the Institute's single technology appraisal (STA) process. Kleijnen Systematic Reviews Ltd (KSR), in collaboration with Erasmus University Rotterdam, was commissioned to act as the Evidence Review Group (ERG). This paper describes the company's submission, the ERG review, and NICE's subsequent decisions. Clinical effectiveness evidence for ramucirumab monotherapy (RAM), compared with best supportive care (BSC), was based on data from the REGARD trial. Clinical effectiveness evidence for ramucirumab combination therapy (RAM + PAC), compared with paclitaxel monotherapy (PAC), was based on data from the RAINBOW trial. In addition, the company undertook a network meta-analysis (NMA) to compare RAM + PAC with BSC and docetaxel. Cost-effectiveness evidence of monotherapy and combination therapy relied on partitioned survival, cost-utility models. The base-case incremental cost-effectiveness ratio (ICER) of the company was £188,640 (vs BSC) per quality-adjusted life-year (QALY) gained for monotherapy and £118,209 (vs BSC) per QALY gained for combination therapy. The ERG assessment indicated that the modelling structure represented the course of the disease; however, a few errors were identified and some of the input parameters were challenged. The ERG provided a new base case, with ICERs (vs BSC) of £188,100 (monotherapy) per QALY gained and £129,400 (combination therapy) per QALY gained and conducted additional exploratory analyses. The NICE Appraisal Committee (AC), considered the company's decision problem was in

  18. Insulin pen needles: effects of extra-thin wall needle technology on preference, confidence, and other patient ratings.

    Science.gov (United States)

    Aronson, Ronnie; Gibney, Michael A; Oza, Kunjal; Bérubé, Julie; Kassler-Taub, Kenneth; Hirsch, Laurence

    2013-07-01

    Pen needles (PNs) are essential for insulin injections using pen devices. PN characteristics affect patients' injection experience. The goal of this study was to evaluate the impact of a new extra-thin wall (XTW) PN versus usual PNs on overall patient preference, ease of injection, perceived time to complete the full dose, thumb button force to deliver the injection, and dose delivery confidence in individuals with diabetes mellitus (DM). Subjects injected insulin with the KwikPen(TM) (Eli Lilly and Company, Indianapolis, Indiana), SoloSTAR(®) (sanofi-aventis U.S. LLC, Bridgewater, New Jersey), and FlexPen(®) (Novo Nordisk A/S, Bagsvaerd, Denmark) insulin pens, and included some with impaired hand dexterity. We first performed quantitative testing of XTW and comparable PNs with the 3 insulin pens for thumb force, flow rate, and time to deliver medication. A prospective, randomized, 2-period, open-label, crossover trial was then conducted in patients aged 35 to 80 years with type 1 or type 2 DM who injected insulin by pen for ≥2 months, with at least 1 daily dose ≥10 U. Patients who used 4- to 8-mm length PNs with 31- to 32-G diameter were randomly assigned to use their current PN or the same/similar size XTW PN at home for ~1 week and the other PN the second week. They completed several comparative 150-mm visual analog scales and direct questions at the end of period 2. XTW PNs had statistically significant better performance for each studied PN characteristic (thumb force, flow, and time to deliver medication) for all pens combined and each individual pen brand (all, P ≤ 0.05). Of 216 patients randomized to study groups (80, SoloSTAR; 77, FlexPen; 59, KwikPen), 209 completed both periods; 198 were evaluable. Baseline characteristics revealed a mean (SD) age of 60.8 (9.3) years, insulin pen use duration of 4.3 (4.1) years, and mean total daily dose of 75.1 (52.3) U (range, 10-420 U). Approximately 50% of patients were female; 81.5% were white and 14.8% were

  19. Powdery mildew of ornamental species caused by Oidiopsis haplophylli in Brazil Oídio em plantas ornamentais, causado por Oidiopsis haplophylli, no Brasil

    Directory of Open Access Journals (Sweden)

    Ailton Reis

    2007-12-01

    Full Text Available Oidiopsis haplophylli (syn. Oidiopsis sicula was identified as the causal agent of powdery mildew diseases occurring on five ornamental species in Brazil. This disease was observed in plastic house-grown lisianthus (Eustoma grandiflorum: Gentianaceae, in nasturtium (Tropaeolum majus: Tropaeolaceae cultivated under open field conditions and in greenhouse-grown calla lily (Zantedeschia aethiopica: Araceae, impatiens (Impatiens balsamina: Balsaminaceae and balloon plant (Asclepias physocarpa: Asclepiadaceae. Typical disease symptoms consisted of chlorotic areas on the upper leaf surface corresponding to a fungal colony in the abaxial surface. With the disease progression, these chlorotic areas eventually turned to necrotic (brown lesions. Fungi morphology on all hosts was similar to that described for the imperfect stage of Leveillula taurica (O. haplophylli. The Koch's postulates were fulfilled by inoculating symptom-free plants via leaf-to-leaf contact with fungal colonies. Additional inoculations using an isolate of O. haplophylli from sweet pepper (Capsicum annuum demonstrated that it is pathogenic to all five species belonging to distinct botanical families, indicating lack of host specialization. This is the first formal report of a powdery mildew disease on lisianthus, calla lilly, impatiens and nasturtium in Brazil. It is, to our knowledge, the first report of O. haplophyllii infecting A. physocarpa, extending the host range of this atypical powdery mildew-inducing fungus. This disease might become important on these ornamental crops especially in protected cultivation and also under field conditions in hot and dry areas of Brazil.O fungo Oidiopsis haplophylli (= O. sicula foi identificado como sendo o agente causal de uma nova doença do tipo oídio em beijo-de-frade (Impatiens balsamina: Balsaminaceae, capuchinha (Tropaeolum majus: Tropaeolaceae, copo-de-leite (Zantedeschia aethiopica: Araceae, lisianthus (Eustoma grandiflorum

  20. Probability of major depression diagnostic classification using semi-structured versus fully structured diagnostic interviews.

    Science.gov (United States)

    Levis, Brooke; Benedetti, Andrea; Riehm, Kira E; Saadat, Nazanin; Levis, Alexander W; Azar, Marleine; Rice, Danielle B; Chiovitti, Matthew J; Sanchez, Tatiana A; Cuijpers, Pim; Gilbody, Simon; Ioannidis, John P A; Kloda, Lorie A; McMillan, Dean; Patten, Scott B; Shrier, Ian; Steele, Russell J; Ziegelstein, Roy C; Akena, Dickens H; Arroll, Bruce; Ayalon, Liat; Baradaran, Hamid R; Baron, Murray; Beraldi, Anna; Bombardier, Charles H; Butterworth, Peter; Carter, Gregory; Chagas, Marcos H; Chan, Juliana C N; Cholera, Rushina; Chowdhary, Neerja; Clover, Kerrie; Conwell, Yeates; de Man-van Ginkel, Janneke M; Delgadillo, Jaime; Fann, Jesse R; Fischer, Felix H; Fischler, Benjamin; Fung, Daniel; Gelaye, Bizu; Goodyear-Smith, Felicity; Greeno, Catherine G; Hall, Brian J; Hambridge, John; Harrison, Patricia A; Hegerl, Ulrich; Hides, Leanne; Hobfoll, Stevan E; Hudson, Marie; Hyphantis, Thomas; Inagaki, Masatoshi; Ismail, Khalida; Jetté, Nathalie; Khamseh, Mohammad E; Kiely, Kim M; Lamers, Femke; Liu, Shen-Ing; Lotrakul, Manote; Loureiro, Sonia R; Löwe, Bernd; Marsh, Laura; McGuire, Anthony; Mohd Sidik, Sherina; Munhoz, Tiago N; Muramatsu, Kumiko; Osório, Flávia L; Patel, Vikram; Pence, Brian W; Persoons, Philippe; Picardi, Angelo; Rooney, Alasdair G; Santos, Iná S; Shaaban, Juwita; Sidebottom, Abbey; Simning, Adam; Stafford, Lesley; Sung, Sharon; Tan, Pei Lin Lynnette; Turner, Alyna; van der Feltz-Cornelis, Christina M; van Weert, Henk C; Vöhringer, Paul A; White, Jennifer; Whooley, Mary A; Winkley, Kirsty; Yamada, Mitsuhiko; Zhang, Yuying; Thombs, Brett D

    2018-06-01

    original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.

  1. AMCP Partnership Forum: Advancing Value-Based Contracting.

    Science.gov (United States)

    2017-11-01

    of a VBC for facilitating discussion with key policy makers and regulators; (b) determine strategies for advancing the development and utilization of performance benchmarks; (c) identify best practices in evaluating, implementing, and monitoring VBCs; and (d) develop action plans to mitigate legal and regulatory barriers to VBCs. More than 30 national and regional health care leaders representing health plans, integrated delivery systems, pharmacy benefit managers, employers, data and analytics companies, and biopharmaceutical companies participated. Speakers, panelists, and stakeholders attended the forum and explored the current environment for VBCs, identified challenges to the expansion of VBCs, offered potential solutions to those challenges, and developed an action plan for addressing selected challenges. The forum recommendations will be used by AMCP to establish a coalition of organizations to seek broader acceptance of VBCs in the marketplace and by policymakers. The recommendations will also help AMCP provide tools and resources to stakeholders in managing VBCs. This Partnership Forum was supported by Amgen, Bristol-Myers Squibb, Eli Lilly, Merck, the National Pharmaceutical Council, Novo Nordisk, Premier, the Pharmaceutical Research and Manufacturers of America, RxAnte, Takeda, and Xcenda.

  2. Immune Protection against Lethal Fungal-Bacterial Intra-Abdominal Infections.

    Science.gov (United States)

    Lilly, Elizabeth A; Ikeh, Melanie; Nash, Evelyn E; Fidel, Paul L; Noverr, Mairi C

    2018-01-16

    trained innate immunity. IMPORTANCE Polymicrobial intra-abdominal infections are clinically devastating infections with high mortality rates, particularly those involving fungal pathogens, including Candida species. Even in patients receiving aggressive antimicrobial therapy, mortality rates remain unacceptably high. There are no available vaccines against IAI, which is complicated by the polymicrobial nature of the infection. IAI leads to lethal systemic inflammation (sepsis), which is difficult to target pharmacologically, as components of the inflammatory response are also needed to control the infection. Our studies demonstrate that prior inoculation with low-virulence Candida species provides strong protection against subsequent lethal infection with C. albicans and S. aureus Surprisingly, protection is long-lived but not mediated by adaptive (specific) immunity. Instead, protection is dependent on cells of the innate immune system (nonspecific immunity) and provides protection against other virulent Candida species. This discovery implies that a form of trained innate immunity may be clinically effective against polymicrobial IAI. Copyright © 2018 Lilly et al.

  3. Geologic map of the Frisco quadrangle, Summit County, Colorado

    Science.gov (United States)

    Kellogg, Karl S.; Bartos, Paul J.; Williams, Cindy L.

    2002-01-01

    : Contributions to Mineralogy and Petrology, v. 67, p. 379-396.). Surficial deposits include (1) an old, deeply dissected landslide deposit, possibly as old as Tertiary, on the south flank of Tenderfoot Mountain, (2) deeply weathered, very coarse gravel deposits, mostly along Gold Run and underlying Mesa Cortina; the gravels are gold bearing and were mined by hydraulic methods in the 1800's, (3) glacial deposits of both Bull Lake (middle Pleistocene) and Pinedale (late Pleistocene) that were derived from large valley glaciers that flowed down Tenmile and North Tenmile Creeks; the town of Frisco is underlain mostly by Pinedale-age glacial outwash, (4) recent landslide deposits, including one large (about 1 square kilometer) area just downslope from Lilly Pad Lake, west of I-70, and (5)extensive colluvial and alluvial deposits. The latest seismic events appear to be middle Pliestocene in age and are associated with small scarps that cut Bull Lake till but do not cut Pinedale till.

  4. Connecting research discovery with care delivery in dementia: the development of the Indianapolis Discovery Network for Dementia

    Directory of Open Access Journals (Sweden)

    Boustani MA

    2012-11-01

    Full Text Available Malaz A Boustani,1–3 Amie Frame,1,2 Stephanie Munger,1,2 Patrick Healey,4 Jessie Westlund,5 Martin Farlow,6,7 Ann Hake,8 Mary Guerriero Austrom,6,9 Polly Shepard,10 Corby Bubp,10 Jose Azar,3 Arif Nazir,3 Nadia Adams,11 Noll L Campbell,1,2,12,13 Azita Chehresa,5 Paul Dexter2,31Indiana University Center for Aging Research, 2Regenstrief Institute, Inc, 3Department of Medicine, Indiana University School of Medicine (IUSM, 4St Vincent Health Network, 5Community Health Network, 6Indiana Alzheimer Disease Center, IUSM, 7Department of Neurology, IUSM, 8Eli Lilly and Company, 9Department of Psychiatry, IUSM, 10The Memory Clinic of Indianapolis, 11Indiana University Health, Indianapolis, IN, USA; 12Department of Pharmacy Practice, Purdue University College of Pharmacy, West Lafayette, IN, USA; 13Department of Pharmacy, Wishard Health Services, Indianapolis, IN, USABackground: The US Institute of Medicine has recommended an integrated, locally sensitive collaboration among the various members of the community, health care systems, and research organizations to improve dementia care and dementia research.Methods: Using complex adaptive system theory and reflective adaptive process, we developed a professional network called the “Indianapolis Discovery Network for Dementia” (IDND. The IDND facilitates effective and sustainable interactions among a local and diverse group of dementia researchers, clinical providers, and community advocates interested in improving care for dementia patients in Indianapolis, Indiana.Results: The IDND was established in February 2006 and now includes more than 250 members from more than 30 local (central Indiana organizations representing 20 disciplines. The network uses two types of communication to connect its members. The first is a 2-hour face-to-face bimonthly meeting open to all members. The second is a web-based resource center (http://www.indydiscoverynetwork.org. To date, the network has: (1 accomplished the

  5. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial.

    Science.gov (United States)

    Wilke, Hansjochen; Muro, Kei; Van Cutsem, Eric; Oh, Sang-Cheul; Bodoky, György; Shimada, Yasuhiro; Hironaka, Shuichi; Sugimoto, Naotoshi; Lipatov, Oleg; Kim, Tae-You; Cunningham, David; Rougier, Philippe; Komatsu, Yoshito; Ajani, Jaffer; Emig, Michael; Carlesi, Roberto; Ferry, David; Chandrawansa, Kumari; Schwartz, Jonathan D; Ohtsu, Atsushi

    2014-10-01

    plus paclitaxel included neutropenia (133 [41%] of 327 vs 62 [19%] of 329), leucopenia (57 [17%] vs 22 [7%]), hypertension (46 [14%] vs eight [2%]), fatigue (39 [12%] vs 18 [5%]), anaemia (30 [9%] vs 34 [10%]), and abdominal pain (20 [6%] vs 11 [3%]). The incidence of grade 3 or higher febrile neutropenia was low in both groups (ten [3%] vs eight [2%]). The combination of ramucirumab with paclitaxel significantly increases overall survival compared with placebo plus paclitaxel, and could be regarded as a new standard second-line treatment for patients with advanced gastric cancer. Eli Lilly and Company. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Spectral Gap Energy Transfer in Atmospheric Boundary Layer

    Science.gov (United States)

    Bhushan, S.; Walters, K.; Barros, A. P.; Nogueira, M.

    2012-12-01

    Experimental measurements of atmospheric turbulence energy spectra show E(k) ~ k-3 slopes at synoptic scales (~ 600 km - 2000 km) and k-5/3 slopes at the mesoscales (theory, it is expected that a strong backward energy cascade would develop at the synoptic scale, and that circulation would grow infinitely. To limit this backward transfer, energy arrest at macroscales must be introduced. The most commonly used turbulence models developed to mimic the above energy transfer include the energy backscatter model for 2D turbulence in the horizontal plane via Large Eddy Simulation (LES) models, dissipative URANS models in the vertical plane, and Ekman friction for the energy arrest. One of the controversial issues surrounding the atmospheric turbulence spectra is the explanation of the generation of the 2D and 3D spectra and transition between them, for energy injection at the synoptic scales. Lilly (1989) proposed that the existence of 2D and 3D spectra can only be explained by the presence of an additional energy injection in the meso-scale region. A second issue is related to the observations of dual peak spectra with small variance in meso-scale, suggesting that the energy transfer occurs across a spectral gap (Van Der Hoven, 1957). Several studies have confirmed the spectral gap for the meso-scale circulations, and have suggested that they are enhanced by smaller scale vertical convection rather than by the synoptic scales. Further, the widely accepted energy arrest mechanism by boundary layer friction is closely related to the spectral gap transfer. This study proposes an energy transfer mechanism for atmospheric turbulence with synoptic scale injection, wherein the generation of 2D and 3D spectra is explained using spectral gap energy transfer. The existence of the spectral gap energy transfer is validated by performing LES for the interaction of large scale circulation with a wall, and studying the evolution of the energy spectra both near to and far from the wall

  7. Dulaglutide as add-on therapy to SGLT2 inhibitors in patients with inadequately controlled type 2 diabetes (AWARD-10): a 24-week, randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Ludvik, Bernhard; Frías, Juan P; Tinahones, Francisco J; Wainstein, Julio; Jiang, Honghua; Robertson, Kenneth E; García-Pérez, Luis-Emilio; Woodward, D Bradley; Milicevic, Zvonko

    2018-05-01

    in patients receiving dulaglutide (least squares mean [LSM] for dulaglutide 1·5 mg -1·34% [SE 0·06] or -14·7 mmol/mol [0·6]; dulaglutide 0·75 mg -1·21% [0·06] or -13·2 mmol/mol [0·6]) than in patients receiving placebo (-0·54% [0·06] or -5·9 mmol/mol [0·6]; pEli Lilly and Company. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Autoportree : [luuletused] / Artur Alliksaar ; [Impressioonid] : Viiu Härm

    Index Scriptorium Estoniae

    Alliksaar, Artur, 1923-1966

    2004-01-01

    Sisu: Autoportree ; Antidolorosum ; Asüül ; Sententse kahesusest (Nefas) ; Üksinduse randadel ; Ootus ; Uskumus ; Pilgud punuvad püüniseid ; Selgimus ; Talveidüll ; Tantsijad ; Sõnade sügis ; Optimistlik eleegia ; Jällenägemine (Quasi una fantasia) ; Kolm unesoolot kuuldamatu kooriga ; Padrikus ; Tundmatu eel ; Õnnelähistel ; Nauding ; Hilissuve päev ; Neis mälestustes pole kahetsust ; Mu hinges mälestused on tõusnud troonile ; Laskumine ; Ahtumine ; Üks sügishommik on äkki vilu... ; Hea oleks teada... ; Salapärane rongkäik ; Janud ; Seitse etüüdi ; Nõiaringis ; Kahe ääretuse vahel...; Õhtu rannas ; Keegi ei tea... (Primitiive) ; Eelärkamine ; Kirjaneitsi mälestuseks ; Friedebert Tuglasele ; Rein Sepale ; Mõttejoomar ; Kolm kunstnikku: Altamira Nimetu ; Vabadus ; Navigaatorid ; Ei hävi mõte, varjav elu seemneid ; Olematus võiks ju ka olemata olla ; Alternatiive ; Ärev on ärkamine äikesesse ; Nokturn, veidi ärev ja veidi kurb ; Ootesaalis ; Päikestepillajad ; Eleegiline ditüramb dialektilise analüüsi elementidega ; Sain siledaks vileda vile, mille kõikainsa aine ja helilained pühendan Ain Kaalepile ; "Santa Maria" ; Ulmfantaasiaid ; Tule, kuula, kuidas kumisevad uned ; Kamalutäis kaaluvihte ; On see õitsvate kaktuste sosin? (Picasso - Magnelli - Mir̤) ; Mis kuulub kõigile, ei kuulu kellelegi ; Tuulefuuga tumma suuga mõtisklusse vajund puuga... ; Välkvisioon ; Kohtumisi ; Lahkühtimine ; Avastusretk ; Lootust peab pälvima ; Kahekesi ; Liturgiline litsents ; Käidi ja külvati varjude seemneid, sest valgus hakkas võrsuma ; Tule, tule tulega! ; Kuigi on nii palju lilli... ; Pöördehetk ; Küsin sinult... ; Armastuse teed on voolavad kui veed ; Sidruniballaad ; Katkeid ; On asju, milles eksida ei saa ; Diletandi mõtteid vabavärsist ; Teeme hüppe laanerüppe kevadmaikudes, iga viga, haigus vaibub vaiguvaikuses (valimik mikrovalme) ; Lüüriline intermetso ; Jagamatu on jagatud ; Välgud peeglis ; Nostalgia ; Tikut

  9. Writers, Athletes and Engineers Learn by Doing

    Science.gov (United States)

    Narayanan, M.

    2009-12-01

    provided evidence-based reasoning and critical thinking. 6. He/She has suggested a time-line for completing the assignment. 7. The person has completed the required process in the alloted time-line. In this presentation the author stresses the importance of writing assignments in engineering disciplines. References: Barr, R. B., & Tagg, J. (1995, November/December). From teaching to learning: A new paradigm for undergraduate education. Change: The Magazine of Higher Education, 13-24. Cox, M. D., Grasha, A., & Richlin, L. (1997, March). Town meeting. Between teaching model and learning model: Adapting and adopting bit by bit. Paper presented at the ninth annual Lilly Conference on College and University Teaching - West, Lake Arrowhead, CA. Narayanan, Mysore (2009). Assessment Based on the principles of Theodore Marchese. ASEE 116th Annual Conference and Exposition, Austin, TX. June 14-17, 2009. Paper # AC 2009-1532. Saxe, S. (1990, June). Peer influence and learning. Training and Development Journal, 42 (6), 50-53. Senge, P. M. (1990). The fifth discipline: The art and practice of the learning organization. New York: Currency Doubleday.

  10. Large Eddy simulation of turbulence: A subgrid scale model including shear, vorticity, rotation, and buoyancy

    Science.gov (United States)

    Canuto, V. M.

    1994-01-01

    latter phenomenon, which affects both geophysical and astrophysical turbulence (e.g., oceanic structure and convective overshooting in stars), has been singularly difficult to account for in turbulence modeling. For example, the widely used model of Deardorff has not been confirmed by recent LES results. As of today, there is no SGS model capable of incorporating buoyancy, rotation, shear, anistropy, and stable stratification (gravity waves). In this paper, we construct such a model which we call CM (complete model). We also present a hierarchy of simpler algebraic models (called AM) of varying complexity. Finally, we present a set of models which are simplified even further (called SM), the simplest of which is the Smagorinsky-Lilly model. The incorporation of these models into the presently available LES codes should begin with the SM, to be followed by the AM and finally by the CM.

  11. [A 50-year history of new drugs in Japan-the development and progress of anti-diabetic drugs and the epidemiological aspects of diabetes mellitus].

    Science.gov (United States)

    Ozawa, Hikaru; Murai, Yuriko; Ozawa, Terutaka

    2003-01-01

    The development and progress of antidiabetic drugs (e.g., insulin preparations and hypoglycemic drugs) are retrospectively investigated in Japan. Their influences on the treatment of diabetes mellitus (DM) and its epidemiological aspects are also discussed. 1) Insulin preparations: Insulin was introduced for DM therapy in 1925, two or three years after its discovery in Canada. The preparations were raw extracts of bovine or porcine pancreas. These did not prevail widely in Japan because of the low incidence of DM before World Wan II. After the war, a shortage of mammalian materials compelled the use of fish pancreatic tissues such as bonito and/or tuna for insulin production. Insulin infection, so-called regular insulin, was first promoted in the 6th "Pharmacopoeia Japonica" (JP6) in 1951 and has been maintained to the present edition (JP14, 2001). Although depot-type insulin preparations were developed in the USA and Europe during the war, the introduction of those preparations to Japan was delayed until 1951, when Protamine zinc insulin appeared. Globin zinc insulin and Isophane insulin were introduced for clinical use in 1952 and 1955, respectively. These were also adopted for JP7 (1961). Biphasic-type insulin, which has a rapid onset and long duration of activity, appeared in 1965. Purified preparations from bovine or porcine sources have been available since 1980, which might be a strong reason for the decrease in insulin allergy. Insulin from animal origin has been supplied for almost 60 years since its discovery. Amino acid sequences of insulins from various species of animals were determined by the pioneering studies of Sanger and his associates. Human insulin, which differs from porcine insulin by only one amino acid, was produced by Novo researchers in 1982 using a semi-synthetic method. Then the Lilly group soon succeeded in obtaining human insulin by recombinant DNA technology in the same year. Both products were introduced to Japan in 1985, and the

  12. A Personalised, Sensor-Based Smart Phone Intervention for Physical Activity and Diet – PRECIOUS N-of-1 Trial

    Directory of Open Access Journals (Sweden)

    Johanna Nurmi

    2015-10-01

    , including reminders, prompts, customised support, measurement, and gamified feedback and reward mechanisms. The novelty of PRECIOUS is based on two factors: (1 a virtual individual model, synthesised from self-reported and sensor parameters, which tailors suggestions to the user, and (2 a motivational service design framework combined with gamification principles to trigger, monitor, and sustain behaviour change, especially designed for individuals with low motivation or intention to act. Aims: This study will establish the feasibility of the PRECIOUS app and examine the effects of various components of PRECIOUS on physical activity with an N-of-1 study design (Lillie et al., 2011. More specifically, the study will identify which service features/behaviour change techniques (BCTs were most used and appreciated by individual users (Michie et al., 2013; investigate whether the use of motivational components leads to greater use of action components, and whether increased use of motivational and action components lead to increases in physical activity. Method/Results: Twelve inactive adults will be recruited to a six-week N-of-1 study testing a new smart phone application and activity bracelet. At baseline and post-treatment, participants will complete questionnaires assessing constructs related to self-determination theory and the health action process approach for both physical activity and healthy eating behaviours, and a 3-day heart rate variability measurement (FirstBeat Ltd; Helsinki, Finland to assess activity level and stress response. Objective physical activity and sleep data will be collected throughout the study using aggregated data gathered from the smartphone’s on-board accelerometer and an activity bracelet. After completion of the study, interviews with participants will qualitatively examine feasibility and acceptability of the interventions and examine possible reasons why the intervention techniques were or were not effective for each participant. The

  13. Racial and Ethnic Disparities in Meeting MTM Eligibility Criteria Based on Star Ratings Compared with the Medicare Modernization Act.

    Science.gov (United States)

    Spivey, Christina A; Wang, Junling; Qiao, Yanru; Shih, Ya-Chen Tina; Wan, Jim Y; Kuhle, Julie; Dagogo-Jack, Samuel; Cushman, William C; Chisholm-Burns, Marie

    2018-02-01

    sensitivity analyses. Disparities were not completely explained by differences in patient characteristics based on the Blinder-Oaxaca approach. The multinomial logistic regression of each main analysis found significant adjusted relative risk ratios (RRR) between whites and blacks for 2009 (RRR = 0.459, 95% CI = 0.438-0.481); 2013 (RRR = 0.449, 95% CI = 0.434-0.465); and 2015 (RRR = 0.436, 95% CI = 0.425-0.446) and between whites and Hispanics for 2009 (RRR = 0.559, 95% CI = 0.528-0.593); 2013 (RRR = 0.544, 95% CI = 0.521-0.569); and 2015 (RRR = 0.503, 95% CI = 0.488-0.518). These findings indicate a significant reduction in racial and ethnic disparities when using star ratings eligibility criteria; for example, black-white disparities in the likelihood of meeting MTM eligibility criteria were reduced by 55.1% based on star ratings compared with MMA in 2013. Similar patterns were found in most sensitivity and disease-specific analyses. This study found that minorities were more likely than whites to be MTM-eligible under the star ratings criteria. In addition, MTM eligibility criteria based on star ratings would reduce racial and ethnic disparities associated with MMA in the general Medicare population and those with specific chronic conditions. Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health under award number R01AG049696. The content of this study is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Cushman reports an Eli Lilly grant and uncompensated consulting for Takeda Pharmaceuticals outside this work. The other authors have no potential conflicts of interest to report. Study concept and design were contributed by Wang and Shih, along with Wan, Kuhle, Spivey, and Cushman. Wang, Qiao, and Wan took the lead in data collection, with assistance from the other authors. Data interpretation was performed by Wang, Kuhle

  14. Prasugrel (Efient®) with percutaneous coronary intervention for treating acute coronary syndromes (review of TA182): systematic review and economic analysis.

    Science.gov (United States)

    Greenhalgh, Janette; Bagust, Adrian; Boland, Angela; Dwan, Kerry; Beale, Sophie; Fleeman, Nigel; McEntee, Joanne; Dundar, Yenal; Richardson, Marty; Fisher, Michael

    2015-04-01

    Acute coronary syndromes (ACSs) are life-threatening conditions associated with acute myocardial ischaemia. There are three main types of ACS: ST segment elevation myocardial infarction (STEMI), non-ST segment elevation myocardial infarction (NSTEMI) and unstable angina (UA). One treatment for ACS is percutaneous coronary intervention (PCI) plus adjunctive treatment with antiplatelet drugs. Dual therapy antiplatelet treatment [aspirin plus either prasugrel (Efient(®), Daiichi Sankyo Company Ltd UK/Eli Lilly and Company Ltd), clopidogrel or ticagrelor (Brilique(®), AstraZeneca)] is standard in UK clinical practice. Prasugrel is the focus of this review. The remit is to appraise the clinical effectiveness and cost-effectiveness of prasugrel within its licensed indication for the treatment of ACS with PCI and is a review of National Institute for Health and Care Excellence technology appraisal TA182. Four electronic databases (MEDLINE, EMBASE, The Cochrane Library, PubMed) were searched from database inception to June 2013 for randomised controlled trials (RCTs) and to August 2013 for economic evaluations comparing prasugrel with clopidogrel or ticagrelor in ACS patients undergoing PCI. Clinical outcomes included non-fatal and fatal cardiovascular (CV) events, adverse effects of treatment and health-related quality of life (HRQoL). Cost-effectiveness outcomes included incremental cost per life-year gained and incremental cost per quality-adjusted life-year (QALY) gained. An independent economic model assessed four mutually exclusive subgroups: ACS patients treated with PCI for STEMI and with and without diabetes mellitus and ACS patients treated with PCI for UA or NSTEMI and with and without diabetes mellitus. No new RCTs were identified beyond that reported in TA182. TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel Thrombolysis in Myocardial Infarction 38) compared prasugrel with clopidogrel in ACS

  15. Laps(epõlv 19. sajandi teise poole Eestis omaelulooliste tekstide näitel. Child(hood in 19th Century Estonia: a Study of Autobiographical Texts

    Directory of Open Access Journals (Sweden)

    Ave Mattheus

    2012-04-01

    Full Text Available In this article I discuss autobiographical texts which focus on children and childhood in late 19th century Estonia. Childhood memories as well as other autobiographical material became popular in Estonia in the 1920s-1930s, when most of the studied works--the memoirs by Anna Haava, Mait Metsanurk, Jaan Lattik, Jaan Vahtra, Friedebert Tuglas, August Kitzberg and Marta Sillaots--were written. Some texts come from the 19th century (e.g. Lilli Suburg’s autobiographical works or early 20th century (e.g. manuscripts by Hans Leoke, and Johannes Kõrv. Childhood as described in these autobiographical texts covers a period of circa 1850-1900, and the majority of the authors come from the families of South-Estonian peasants or manorial servants. In addition to being written in Estonian and having the same theme, they were all also written by authors of fiction for children or by people who had close contact with children, such as schoolteachers. The article offers a novel approach in the Estonian context by presenting a typology of childhood stories and looking at childhood recollections as an important part of childhood studies. The researchers of childhood investigate how society understands and values children and childhood, what children’s everyday life is like, what possibilities there are for development and if there exists a specific children’s culture in society (such as clothing, food, language, leisure activities, or independent creative work. Childhood studies as a separate discipline does not exist in Estonia, although some important works have been published by educational scholars and art historians. The autobiographical texts under discussion show that in the late 19th century, the majority of Estonian children lived in the countryside in patriarchal families, and childhood was short because children had to help their parents with farmwork quite early, at the age of six. The boundary of childhood was around the age of 10-11, when

  16. Book Reviews

    Directory of Open Access Journals (Sweden)

    R. de Ridder

    1986-01-01

    + 182 pp. - Anke Niehof, Imke Swart, Die Traditionellen Grundlagen der Erziehung im Zentralen Java, Wiesbaden: Franz Steiner Verlag, 1983. (130 pp. - J.H.B. den Ouden, R.S. Khare, The untouchable as himself. Ideology, identity and pragmatism among the Lucknow Chamars, Cambridge studies in cultural systems, Cambridge University Press, 1984. - Rien Ploeg, James A. Boon, Other tribes, other scribes; symbolic anthropology in the comparitive study of cultures, histories, religions, and texts, Cambridge: Cambridge University Press, 1982. xiv + 303 pp., appendixes. - Frank N. Pieke, Rubie S. Watson, Inequality among brothers: Class and kinship in South China, Cambridge: Cambridge University Press, 1985. xiii + 193 pp., 3 maps. - Rien Ploeg, Durk Hak, Watching the seaside. Essays on maritime anthropology. A. H. J. Prins; Festschrift on the occasion of his retirement from the Chair of Anthropology, University of Groningen, University of Groningen, 1984, 251 pp., ill., diagr., Ybeltje Kroes, Hans Schneymann (eds. - Rien Ploeg, Ladislav Holy, Actions, norms and representations. Foundations of anthropological inquiry. Cambridge: Cambridge University Press, 1983. VIII + 134 pp., Milan Stuchlik (eds. - Rien Ploeg, Nancy L. Hamblin, Animal use by the Cozumel Maya, Tucson, Arizona: The University of Arizona Press, 1984. 206 pp. - Ronald H. Poelmeijer, Lilly Eversdijk Smulders, Een jaar bij de yogiýs van India en Tibet, Deventer 1983. - Ype H. Poortinga, Dean Peabody, National characteristics, Cambridge/Paris: Camnbridge University Press/Editions de la Maison des Sciences de lýHomme, 1985. - Karen Portier, Khin Thitsa, Nuns, mediums and prostitutes in Chiengmai: A study of some marginal categories of women (41 pp.. - Karen Portier, Signe Howell, Chewong women in transition: The effects of monetization on a hunter-gatherer society in Malaysia (34 pp.. - Karen Portier, Maila Stivens, Sexual politics in Rembau: Female autonomy, matriliny and agrarian change in Negeri Sembilan, Malaysia

  17. London forum targets Africa's cancer crisis

    International Nuclear Information System (INIS)

    2007-01-01

    meeting, which will be chaired by Alan Milburn, former UK Secretary of State for Health. One of the key speakers is Hilary Benn, UK Secretary of State for International Development. Cancer Control in Africa is limited to 140 delegates. Those attending are central to the implementation of cancer strategies. They include 19 African Health Ministries, from Benin, Botswana, Burkina Faso, Burundi, Cameroon, Cape Verde, Gabon, Ghana, Lesotho, Libya, Malawi, Mauritius, Morocco, Mozambique, Nigeria, Rwanda, Sierra Leone, Uganda and Zambia. Also invited are leading African doctors and health professionals, many of the world's foremost oncologists, UK government members and advisors, cancer organizations and charities (World Health Organization (WHO), International Network for Cancer Treatment and Research (INCTR), U.S. National Cancer Institute (NCI), American Cancer Society (ACS), International Union Against Cancer (UICC), African Organization for Research and Training in Cancer (AORTIC), National Cancer Research Institute, UK, Breakthrough Breast Cancer, African Palliative Care Association and Help the Hospices), representatives from the pharmaceutical industry (GSK, Roche, Novartis, GE Healthcare and Eli Lilly), the Gates Foundation, the African Development Bank and investment bankers. There will be two press briefings: Venue: Committee Room, The Reform Club, 104 Pall Mall, London, SW1Y 5EW. Times: Thursday, 10 May, 09:00-10:00 and Friday, 11 May, 16:00-17:00. Space is limited to 25 journalists per briefing. Advance registration is therefore requested. (IAEA)

  18. Baricitinib for Previously Treated Moderate or Severe Rheumatoid Arthritis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

    Science.gov (United States)

    Ren, Shijie; Bermejo, Iñigo; Simpson, Emma; Wong, Ruth; Scott, David L; Young, Adam; Stevenson, Matt

    2018-03-03

    As part of its single technology appraisal process, the National Institute for Health and Care Excellence invited the manufacturer (Eli Lilly) of baricitinib (BARI; Olumiant ® ; a Janus kinase inhibitor that is taken orally) to submit evidence of its clinical and cost effectiveness for the treatment of moderate to severe rheumatoid arthritis (RA) after the failure of disease-modifying antirheumatic drugs (DMARDs). The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a detailed review of the evidence for the clinical and cost effectiveness of the technology, based on the company's submission (CS) to NICE. The clinical-effectiveness evidence in the CS for BARI was based predominantly on three randomised controlled trials comparing the efficacy of BARI against adalimumab or placebo, as well as one long-term extension study. The clinical-effectiveness review identified no head-to-head evidence on the efficacy of BARI against all the comparators within the scope. Therefore, the company performed network meta-analyses (NMAs) in two different populations: one in patients who had experienced an inadequate response to conventional DMARDs (cDMARD-IR), and the other in patients who had experienced an inadequate response to tumour necrosis factor inhibitors (TNFi-IR). The company's NMAs concluded BARI had comparable efficacy as the majority of its comparators in both populations. The company submitted a de novo discrete event simulation model that analysed the incremental cost-effectiveness of BARI versus its comparators for the treatment of RA from the perspective of the National Health Service (NHS) in four different populations: (1) cDMARD-IR patients with moderate RA, defined as a 28-Joint Disease Activity Score (DAS28) > 3.2 and no more than 5.1; (2) cDMARD-IR patients with severe RA (defined as a DAS28 > 5.1); (3) TNFi-IR patients

  19. Ixekizumab for Treating Moderate-to-Severe Plaque Psoriasis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

    Science.gov (United States)

    Ramaekers, Bram L T; Wolff, Robert F; Pouwels, Xavier; Oosterhoff, Marije; Van Giessen, Anoukh; Worthy, Gill; Noake, Caro; Armstrong, Nigel; Kleijnen, Jos; Joore, Manuela A

    2018-02-26

    The National Institute for Health and Care Excellence invited Eli Lilly and Company Ltd, the company manufacturing ixekizumab (tradename Taltz ® ), to submit evidence for the clinical and cost effectiveness of ixekizumab. Ixekizumab was compared with tumour necrosis factor-α inhibitors (etanercept, infliximab, adalimumab), ustekinumab, secukinumab, best supportive care and, if non-biological treatment or phototherapy is suitable, also compared with systemic non-biological therapies and phototherapy with ultraviolet B radiation for adults with moderate-to-severe plaque psoriasis. Kleijnen Systematic Reviews Ltd, in collaboration with Maastricht University Medical Center, was commissioned as the independent Evidence Review Group. This article presents a summary of the company submission, the Evidence Review Group report and the development of the National Institute for Health and Care Excellence guidance for the use of this drug in England and Wales by the Appraisal Committee. The Evidence Review Group produced a critical review of the clinical and cost effectiveness of ixekizumab based on the company submission. The company submission presented three randomised controlled trials identified in a systematic review. All randomised controlled trials were phase III, multicentre placebo-controlled trials including 3866 participants with moderate-to-severe psoriasis. Two trials also included an active comparator (etanercept). All randomised controlled trials showed statistically significant increases in two primary outcomes, static Physician Global Assessment (0,1) and improvement of 75% from baseline in the Psoriasis Area and Severity Index. Ixekizumab was generally well tolerated in the randomised controlled trials, with similar discontinuation rates because of adverse events as placebo or etanercept. The most frequent adverse events of special interest were infections and injection-site reactions. The company submission also included a network meta-analysis of

  20. Antisense oligodeoxynucleotide inhibition as a potent diagnostic tool for gene function in plant biology

    Energy Technology Data Exchange (ETDEWEB)

    Jansson, Christer; Sun, Chuanxin; Ghebramedhin, Haile; Hoglund, Anna-Stina; Jansson, Christer

    2008-01-15

    -signaling proteins in pollen tubes from the lilly Agapanthus umbellatus. For the uptake of DNA pollen tubes represent a unique system since the growing tip is surrounded by a loose matrix of hemicellulose and pectins, exposing the plasma membrane7 and the first uptake of ODNs by pollen tubes was reported as early as 1994. A breakthrough in the employment of antisense ODN inhibition as a powerful approach in plant biology was recently presented through our work on intact barley leaves. As was illustrated by confocal microscopy and fluorescently labeled ODNs, naked ODNs were taken up through the leaf petiole and efficiently imported into the plant cell and the nucleus. The work portrayed in that study demonstrate the applicability of antisense ODN inhibition in plant biology, e.g. as a rapid antecedent to time-consuming transgenic studies, and that it operates through RNase H degradation. We employed the antisense ODN strategy to demonstrate the importance of the SUSIBA2 transcription factor in regulation of starch synthesis, and to depict a possible mechanism for sugar signaling in plants and how it might confer endosperm-specific gene expression during seed development. We also described the employment of the antisense ODN strategy for studies on in vitro spike cultures of barley. Here we present further evidence as to the value of the antisense ODN approach in plant biology by following the effects on starch branching enzyme (SBE) accumulation in barley leaves after suppression of individual SBE genes. In agreement with transcript analyses of SBE expression in barley leaves, a zymogram assay (Fig. 1) revealed that sucrose treatment of barley leaves increased the number of SBE activity bands as compared to sorbitol treatment. In the presence of antisense SBEI or SBEIIA ODNs, zymograms of sucrose-treated leaves displayed only a subset of these activities with bands in the top portion of the zymogram gel missing or diminished. With antisense SBEIIB ODN, all activity bands in the top

  1. Optimizing Anti-VEGF Treatment Outcomes for Patients with Neovascular Age-Related Macular Degeneration.

    Science.gov (United States)

    Wykoff, Charles C; Clark, W Lloyd; Nielsen, Jared S; Brill, Joel V; Greene, Laurence S; Heggen, Cherilyn L

    2018-02-01

    advisory board work with Nestle Health Sciences, Indivior Pharmaceuticals, Eli Lilly, Blue Earth Diagnostics, Bayer, and AstraZeneca. Nielson reports advisory board work/consultancy and research grants for Genentech/Roche; advisory board work and research grants from Regeneron; and research grants from Alcon and Ophthotech.

  2. Cetuximab plus carboplatin and paclitaxel with or without bevacizumab versus carboplatin and paclitaxel with or without bevacizumab in advanced NSCLC (SWOG S0819): a randomised, phase 3 study.

    Science.gov (United States)

    Herbst, Roy S; Redman, Mary W; Kim, Edward S; Semrad, Thomas J; Bazhenova, Lyudmila; Masters, Gregory; Oettel, Kurt; Guaglianone, Perry; Reynolds, Christopher; Karnad, Anand; Arnold, Susanne M; Varella-Garcia, Marileila; Moon, James; Mack, Philip C; Blanke, Charles D; Hirsch, Fred R; Kelly, Karen; Gandara, David R

    2018-01-01

    -cell carcinoma cancers are encouraging and support continued evaluation of anti-EGFR antibodies in this subpopulation. National Cancer Institute and Eli Lilly and Company. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. The Clinical Observation of Music Therapy in Combination Chinese Medicine in Treating Depression due to Malignant Tumor%五音疗法联合中药治疗恶性肿瘤抑郁症临床观察

    Institute of Scientific and Technical Information of China (English)

    温微微; 刘东波; 殷德科

    2017-01-01

    Objective:To observe the clinical curative effect of music therapy in combination with Chinese medicine in treating depression due to malignant tumor.Methods:Sixty patients with depression due to malignant tumor were randomly divided into A treatment group,B control group,C control group,20 cases in each group.The ones in the treatment group A adopted music therapy in combination with Chinese medicine listening to the corresponding music according to different syndrome.once a day,24 minutes each time,and regarding 3 weeks as one course.At the same time,they took Chinese medicine decoction orally according to different types,one dose each day,400 Ml each time which was divided into two parts.The ones in the B control group were treated with Chinese medicine,such as Modified Danzhi Xiaoyao Powder (DZXYS) for syndrome of qi stagnation generating fire,Modified Celestial Emperor Heart-Supplementing Elixir for syndrome of heart-yin deficiency,Modified Spleen-Restoring Decoction for syndrome of heart-spleen deficiency,Modified Zishui Qinggan Yin (ZSQGY) for syndrome of liver-spleen yin deficiency,Modified Licorice and Wheat and Jujube Decoction for syndrome of mind confusion.The ones in the C control group were treated with 20 mg of Fluoxetine Capsules (made by Eli Lilly Suzhou Pharmaceutical Co.,Ltd.,J20130010) for oral administration,once a day.and 4 weeks were regarded as one course.After one month's treatment,the clinical curative effect was estimated.Results:The effective rate of A treatment group was 90.00%,while that of the B control group was 65%,that of the C control group was 60%;The difference in efficiency between A group and B control group and C control group was statistically significant(P < 0.05).The difference in efficiency between B control group and C control group was not statistically significant (P > 0.05).After the treatment,the improvements of HAMD score and Karnofsky score in A treatment group were all better than those of B control

  4. Neoadjuvant plus adjuvant bevacizumab in early breast cancer (NSABP B-40 [NRG Oncology]): secondary outcomes of a phase 3, randomised controlled trial.

    Science.gov (United States)

    Bear, Harry D; Tang, Gong; Rastogi, Priya; Geyer, Charles E; Liu, Qing; Robidoux, André; Baez-Diaz, Luis; Brufsky, Adam M; Mehta, Rita S; Fehrenbacher, Louis; Young, James A; Senecal, Francis M; Gaur, Rakesh; Margolese, Richard G; Adams, Paul T; Gross, Howard M; Costantino, Joseph P; Paik, Soonmyung; Swain, Sandra M; Mamounas, Eleftherios P; Wolmark, Norman

    2015-09-01

    Institutes of Health, Genentech, Roche Laboratories, Lilly Research Laboratories, and Precision Therapeutics. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Especially for High School Teachers

    Science.gov (United States)

    Howell, J. Emory

    1999-08-01

    Care to Share? An Informal Syllabus Exchange A recent email message from Thomas Shiland, who teaches at Saratoga Springs Senior High School, noted that the process of revising the high school chemistry syllabus is underway in New York State. He expressed a strong interest in helping construct a chemistry syllabus that represents the best thinking about appropriate content. He wondered if it would be possible to develop a way in which different secondary chemistry syllabi could easily be exchanged. It is likely that readers from other states and countries are involved in a similar process and might also be interested in exchanging syllabi. Many states do not use the term syllabus to describe their guiding curricular document for chemistry but rather refer to it as a framework or as guidelines. In most cases, the document includes a list of key ideas or topics, performance indicators, and the major understandings associated with each key idea. Such documents would be appropriate for exchange among those of you involved in the revision process. If you are interested in arranging an exchange please contact me by email at j.e.howell@usm.edu or by mail at J. E. Howell, Box 5043, USM, Hattiesburg, MS39406-5043, USA. High School Day Information The High School Chemistry Program at the American Chemical Society National Meeting in New Orleans, Louisiana will be held Sunday, August 22, 1999, at the Doubletree Hotel, 300 Canal Street. If you wish to register only for the High School Day activities, which includes a pass to the ACS Exposition, a special registration form is available from Lillie Tucker-Akin, 2800 Reynard Dr., Tupelo, MS38801; sci4me@aol.com; fax: 662/566-7906. Advance registration is 25 and the cost of the High School Luncheon is 12. Register in advance by August 1, 1999, or from 7:45 to 8:30 a.m. at the High School Day table in the conference room area of the Doubletree. The workshop schedule is shown below. Secondary School Feature Articles * Exploring the

  6. London forum targets Africa's cancer crisis

    International Nuclear Information System (INIS)

    2007-01-01

    meeting, which will be chaired by Alan Milburn, former UK Secretary of State for Health. One of the key speakers is Hilary Benn, UK Secretary of State for International Development. Cancer Control in Africa is limited to 140 delegates. Those attending are central to the implementation of cancer strategies. They include 19 African Health Ministries, from Benin, Botswana, Burkina Faso, Burundi, Cameroon, Cape Verde, Gabon, Ghana, Lesotho, Libya, Malawi, Mauritius, Morocco, Mozambique, Nigeria, Rwanda, Sierra Leone, Uganda and Zambia. Also invited are leading African doctors and health professionals, many of the world's foremost oncologists, UK government members and advisors, cancer organizations and charities (World Health Organization (WHO), International Network for Cancer Treatment and Research (INCTR), U.S. National Cancer Institute (NCI), American Cancer Society (ACS), International Union Against Cancer (UICC), African Organization for Research and Training in Cancer (AORTIC), National Cancer Research Institute, UK, Breakthrough Breast Cancer, African Palliative Care Association and Help the Hospices), representatives from the pharmaceutical industry (GSK, Roche, Novartis, GE Healthcare and Eli Lilly), the Gates Foundation, the African Development Bank and investment bankers. There will be two press briefings: Venue: Committee Room, The Reform Club, 104 Pall Mall, London, SW1Y 5EW. Times: Thursday, 10 May, 09:00-10:00 and Friday, 11 May, 16:00-17:00. Space is limited to 25 journalists per briefing. Advance registration is therefore requested. (IAEA) [fr

  7. Especially for High School Teachers

    Science.gov (United States)

    Emory Howell, J.

    1999-11-01

    many of our readers. The High School/College Interface Luncheon was part of the very rich day-long High School Program at the New Orleans ACS Meeting. Shown here (from left) are Glenn Crosby, the luncheon speaker; Lillie Tucker-Akin, the High School Day program chair; and Fred Johnson, Assistant Superintendent of Shelby County (TN) schools and Immediate Past President of NSTA. The recipient of the James Bryant Conant Award in High School Chemistry Teaching is Frank G. Cardulla, who taught for many years at Niles North High School, Skokie, Illinois. His extensive record of service to fellow teachers includes editing the JCE "View from My Classroom" feature for several years and writing several articles, as well as his recent appointment to the JCE Board of Publication. The recipient of the George C. Pimentel Award in Chemical Education is Jerry A. Bell of the American Chemical Society in Washington, DC. An author of numerous articles appearing in JCE and a member of the JCE Board of Publication for several years, he currently serves as Board Chair. The 16th Biennial Conference on Chemical Education Readers who attended the 15th BCCE in Waterloo, Ontario, know that much of the programming at these conferences is of interest to high school teachers. Many work shops, papers, and demonstrations are presented by high school teachers. There are many other outstanding papers and posters, plenary speakers, and exciting demonstrations. The 16th BCCE will be held at the University of Michigan in Ann Arbor, July 30-August 3, 2000. Among the high school teachers already scheduled to present workshops at the 16th BCCE are George Hague, Lynn Hershey, and Jack Randall, and there will be many more before the program is completed. The High School Chemistry Program Chair is Tim Graham, Roosevelt High School (MI). The Organizing Committee is seeking the assistance of local sections of the American Chemical Society within a 300-mile radius of Ann Arbor in providing support for high school

  8. New ways of insulin delivery.

    Science.gov (United States)

    Heinemann, L

    2011-02-01

    The predominant number of papers published from the middle of 2009 to the middle of 2010 about alternative routes of insulin administration (ARIA) were still about inhaled insulin. Long-term experience with Exubera was the topic of a number of publications that are also of relevance for inhaled insulin in general. The clinical trials performed with AIR insulin by Eli Lilly were published in a supplement issue of one diabetes technology journal and most of these will be presented. A number of other publications (also one in a high ranked journal) about their inhaled insulin were from another company: MannKind. The driving force behind Technosphere insulin (TI) - which is the only one still in clinical development - is Al Mann; he has put a lot of his personal fortune in this development. We will know the opinion of the regulatory authorities about TI in the near future; however, I am personally relatively confident that the Food and Drug Administration will provide TI with market approval. The more critical question for me is: will diabetologists and patients jump on this product once it becomes commercially available? Will it become a commercial success? In view of many negative feelings in the scientific community about inhaled insulin, it might be of help that MannKind publish their studies with TI systematically. Acknowledging being a believer in this route of insulin administration myself, one has to state that Exubera and AIR insulin had not offered profound advantages in terms of pharmacokinetic (PK) and pharmacodynamic (PD) properties in comparison with subcutaneously (SC) applied regular human insulin (RHI) and rapid-acting insulin analogues. The time-action profiles of these inhaled insulins were more or less comparable with that of rapid-acting insulin analogues. This is clearly different with TI which exhibits a strong metabolic effect shortly after application and a rapid decline in the metabolic effect thereafter; probably the duration of action is

  9. Obituary: Gary Lars Grasdalen, 1945-2003

    Science.gov (United States)

    Strom, Stephen Eric

    2003-12-01

    With the passing of Gary Grasdalen on 20 April 2003 the astronomical community has lost one its most creative members. Born in Albert Lea, Minnesota on 7 October 1945 to the farming family of Lars G. and Lillie Grasdalen, Gary developed a strong childhood interest in science, and a particular fascination with astronomy. In 1964, he entered Harvard College intending to pursue those interests. During his freshman year, Gary enrolled in an undergraduate research seminar in which he first displayed the combination of keen insight and imagination in applying new techniques that was manifest throughout his professional career. In 1968, he published his first two papers---studies of the C12/C13 ratio in metal deficient stars, and of Fe I and Fe II transition probabilities---which summarized research carried out during his junior and senior years at Harvard. Grasdalen next entered the astronomy graduate program at the University of California, Berkeley. There he developed a strong interest in the early stages of stellar evolution and, in particular, the potential of S-1 image intensifiers and newly available near-infrared detectors to detect and analyze the stellar populations embedded within their parent molecular cloud complexes. Following award of his PhD in 1972, Grasdalen was appointed to the staff at the Kitt Peak National Observatory. Early in his career at KPNO, Gary developed tools that enabled routine near-infrared mapping of nearby molecular cloud complexes, most notably the telescope control programs that enabled precise raster scanning of these regions. Those same programs were some of the many innovations in which Gary had a hand. These innovations enabled a generation of KPNO observers in the 1970s to fully exploit the power of the newly commissioned Mayall telescope as well as the smaller telescopes on Kitt Peak. In 1973, he published the first map of the central region of a molecular cloud, which revealed an extensive embedded, optically obscured

  10. Guidelines, editors, pharma and the biological paradigm shift.

    Science.gov (United States)

    Singh, Ajai R; Singh, Shakuntala A

    2007-01-01

    Private investment in biomedical research has increased over the last few decades. At most places it has been welcomed as the next best thing to technology itself. Much of the intellectual talent from academic institutions is getting absorbed in lucrative positions in industry. Applied research finds willing collaborators in venture capital funded industry, so a symbiotic growth is ensured for both.There are significant costs involved too. As academia interacts with industry, major areas of conflict of interest especially applicable to biomedical research have arisen. They are related to disputes over patents and royalty, hostile encounters between academia and industry, as also between public and private enterprise, legal tangles, research misconduct of various types, antagonistic press and patient-advocate lobbies and a general atmosphere in which commercial interest get precedence over patient welfare.Pharma image stinks because of a number of errors of omission and commission. A recent example is suppression of negative findings about Bayer's Trasylol (Aprotinin) and the marketing maneuvers of Eli Lilly's Xigris (rhAPC). Whenever there is a conflict between patient vulnerability and profit motives, pharma often tends to tilt towards the latter. Moreover there are documents that bring to light how companies frequently cross the line between patient welfare and profit seeking behaviour.A voluntary moratorium over pharma spending to pamper drug prescribers is necessary. A code of conduct adopted recently by OPPI in India to limit pharma company expenses over junkets and trinkets is a welcome step.Clinical practice guidelines (CPG) are considered important as they guide the diagnostic/therapeutic regimen of a large number of medical professionals and hospitals and provide recommendations on drugs, their dosages and criteria for selection. Along with clinical trials, they are another area of growing influence by the pharmaceutical industry. For example, in a

  11. News & Announcements

    Science.gov (United States)

    1999-09-01

    for travel awards for post-doctoral, graduate, and undergraduate women to make their first research presentation at a national meeting sponsored by Eli Lilly & Co. For more information and an application form, contact your department chair; http://www.tamug.tamu.edu/ascwcc; or Cheryl Brown, ACS, 1155 16th Street, NW, Washington, DC 20036; phone: 800/227-5558 ext. 6022; email c_brown@acs.org. The deadline for receipt of applications for meetings between January 1 and June 30, 2000, is October 15, 1999; for meetings between July 1 and December 31, 2000, the deadline is March 15, 2000. Call for Symposia, Papers, Workshops: 16th BCCE The 16th Biennial Conference on Chemical Education will be held July 30­August 3, 2000, at the University of Michigan in Ann Arbor. The conference Web site at http://www.umich.edu/ bcce is ready to accept proposals for symposia, papers, posters, and workshops. Or proposals may be submitted in writing to the Program Chair, Brian Coppola, phone: 734/764-7329; email: bcoppola@umich.edu. The deadline for submission of proposals for symposia and workshops is December 13, 1999; the deadline for submission of abstracts of papers and posters is February 4, 2000. For general information contact Seyhan Ege, phone: 734/764-7340; email: snege@umich.edu. 16th IUPAC Conference on Chemical Thermodynamics 16th IUPAC Conference on Chemical Thermodynamics (concurrent with 55th Calorimetry Conference and 10th Symposium on Thermodynamics of Nuclear Materials) August 6­11, 2000 Halifax, Nova Scotia, Canada This conference will cover research topics in all areas of thermodynamics. In addition, there will be a special poster session for papers on two aspects of thermodynamics education: lecture demonstrations and undergraduate laboratory experiments. Come and join us for lobster and learn what is new and exciting in thermodynamics. To be on the email list for this meeting, send a message to: ICCT@IS.DAL.CA. For further details, consult the conference Web site